A detailed serological analysis of a xenogeneic anti-Ia serum

Rabbit anti-mouse-Ia serum was raised against Ia specificities present in CBAJH (H-2 _k) serum. This xenogeneic antiserum was considered to react with similar specificities to those detected by mouse anti-Ia^k alloantisera and more evidence is now presented for this contention. By absorption, the xenogeneic antiserum was found to react with spleen, lymph node, bone marrow, and thymus, reactions similar to that found with the allogeneic anti-Ia^k antiserum. Furthermore, red cells, platelets, brain, kidney, and liver could not absorb the activity from the xenogeneic antiserum, demonstrating the selective tissue distribution of the antigens reactive with this serum. This reactive population was previously shown to consist of B cells and a subpopulation of T cells. In a backcross study of (C57BL/6 × A)F₁ × C57BL/6, the rabbit anti-Ia and mouse anti-Ia reactions were found to segregate together, and some evidence for the genetic regulation of the expression of Ia specificities was also found. By direct testing, and by absorption testing using a number of strains, the xenogeneic antiserum was shown to contain high titers of antibody to Ia.1, 3, 7, 15, and 17; lower titers to Ia.19, and 22; little antibody to Ia.18, and no reaction for the private specificity Ia. 2, although the multiple absorptions required to define these specificities may have observed some reactions. The data indicate that the xenogeneic and allogeneic anti-Ia_k antisera recognize similar Ia determinants, which map to theLA, IE andIC subregions of theH-2 complex. These have been given the same specificity designation as the allogeneic specificities, but they are separately identified by a prime (').     

Lymphocytes express Ia antigens of foreign haplotype following treatment with neuraminidase

Evidence is presented which indicates that neuraminidase (NA) treatment of spleen cells both destroys old Ia antigens and reveals new Ia specificities which are not normally expressed by splenocytes. It was found that NA treatment unmasked alien I-A^k-like specificities on A.TH (I ^s ) spleen cells, and I^s-like antigens on A.TL (I ^k ) spleen cells. These conclusions were based on direct testing of NA-treated targets with a range of alloantisera and on cell-absorption experiments. Furthermore, the cellular distribution of NA-exposed antigens resembled that of convential Ia antigens, the new antigens being expressed on more than 90 percent of splenic B cells and a subpopulation of splenic T cells. However, although some of the antigens exposed by NA on A.TH cells appeared to resemble the Ia. 3 and 15 specificities, additional antigens were involved which did not correlate with any previously described Ia antigens.Sugar inhibition experiments demonstrated the NA-exposed antigens to be carbohydrate in nature, D-galactose being an effective inhibitor in these studies. The proportion of- and-linked D-galactose residues associated with the new antigens depended upon the target cell used and the anti-Ia serum tested. Furthermore, glycolipid extracts from lymphoid cells were shown to contain the NA-exposed antigens.Collectively, these results support the existence of carbohydrate-defined Ia antigens. The simplest interpretation of the findings is that NA clips off terminal sialic acid residues from carbohydrate-defined Ia antigens on the cell surface and exposes subterminal sugars which resemble antigens expressed by otherI-region haplotypes.     

Serological and biochemical characterization of rat (RT1) class II molecules with restricted mouse anti-Ia sera

Murine anti-Ia sera were tested for their reactivity with rat peripheral lymphocytes. Extensive cross-reactions were observed in a complement-dependent cytotoxicity assay. In the majority of strain combinations, these reactions were specific for B cells. We demonstrated by absorption analyses that (1) the reaction was specific, (2) B cells from all rat strains reacted with anti-I-E^k serum, and (3) the anti-I-A sera defined five new specificities. These antisera can also immunoprecipitate class II (Ia-like) molecules from radiolabeled, detergent-solubilized cell extracts. The rat equivalents of molecules encoded in the I-A and I-E subregions in mice can be isolated from all rat strains studied. The and subunits of the rat class II molecules were polymorphic when analyzed by sodium dodecyl sulfate (SIDS) polyacrylamide electrophoresis. This observation allows the characterization of rat alloantisera or monoclonals of unknown specificity by comparing them to the defined reactivity of the mouse anti-Ia sera.     

Comparison of antigens recognized by xenogeneic and allogeneic anti-Ia antibodies: Evidence for two classes of Ia antigens

Previously published data suggest that both xenogeneic and allogeneic anti-Ia sera can recognize carbohydrate-defined antigenic determinants on the surface of lymphocytes. There is also evidence, based on studies with allogeneic anti-Ia sera, that protein-defined Ia antigens exist. In this paper the relationship between these two types of Ia antigen was examined. It was found that in capping studies, the allogeneic anti-Ia serum could cap off the antigens recognized by the xenogeneic antiserum, whereas the xenogeneic antibodies could, at least partially, clear the surface of lymphocytes of Ia antigens detected by the allogeneic antibodies. On the other hand, when immunoprecipitates of radioiodinated cell-surface antigens were examined by SDS-polyacrylamide-gel electrophoresis, it was found that the xenogeneic anti-Ia serum did not immunoprecipitate any labeled material. In contrast, the allogeneic antiserum immunoprecipitated a labeled molecule which corresponded to the protein-defined Ia antigen described by others. Finally, it was shown that serum Ia antigens could be bound by either mouse or rabbit anti-Ia antibody, and this binding blocked any further reactivity with either serum. These results were interpreted as suggesting that two separate classes of Ia antigen molecule appear on the lymphocyte surface-one class has carbohydrate-defined antigenic specificities and the other has protein-defined determinants. Allogeneic anti-Ia sera contain antibodies against both these antigenic systems, whereas xenogeneic sera recognize only the carbohydratedefined series. The genetic implications of this interpretation are discussed.     

Alterations in the expression of Ia antigens in F1 hybrid mice

The Ia.8 and 9 specificities detected either by conventional or monoclonal antisera (Ia.m3, 4) are present in strains bearing the b H-2 haplotype, but absent from those with the k haplotype. It would be expected that the (b x k)F₁ hybrids would have approximately half the amount of these specificities found on the b parent, but the Ia.8 and 9 specificities are absent or reduced in this F₁ hybrid, though not on F₁ LPS blasts. Examination of appropriate H-2 congenic strains demonstrated that only the k haplotype confers the absence of these specificities on H-2 ^b — it was not observed with b, d, q, r or s haplotypes. In the k haplotype the gene(s) responsible for this effect is mapped to the I-A ^k subregion. The reason for this low expression effect is not clear but the observation has important implications for the relationship of Ia specificities and Ir genes and may serve to explain the low responder status of certain F₁ hybrids, e. g., to TNP-mouse serum albumin, as observed elsewhere.     

Analysis of human class I antigens by two-dimensional gel electrophoresis

Class I antigens were isolated by immunoprecipitation from cell extracts prepared from mitogenically stimulated and internally radiolabeled peripheral blood lymphocytes (PLBs). The precipitating antibodies used are monomorphic and recognize a determinant on the heavy chain of HLA-A, B, C antigens regardless of their allelic specificities when complexed with ₂m, or determinants on ₂m itself. Comparison of class I molecules isolated from 25 different homozygous typing cels (HTC) and analyzed by two-dimensional (2-D) gel electrophoresis allowed the identification of those HLA-A,13 locus specificities most common in the European Caucasoid population. Class I antigens isolated from HTC that are HLA identical are biochemically indistinguishable also. Evidence was obtained for the expression of additional class I antigens besides the HLA-A, B, C locus products: for some haplotypes, up to six class I genes may be active in mitogenically activated PBLs. No differences in molecular weight and isoelectric point of the class I heavy chains were observed between the antigens recognized by W6/32, the anti-heavy chain reagent, and anti- ₂m reagents. The nature of the mitogenic stimulus, i. e., pokeweed mitogen or phytohemagglutinin, was irrelevant with respect to the class I antigens isolated by this method. Using the HTCs as reference, a panel of HLA-B27 positive heterozygous cells was analyzed. Two types of HLA-B27 antigens, distinct by CML typing were represented. These two forms differed also in their biochemical properties. In addition, we obtained evidence for the existence of an A2 variant. This finding was likewise confirmed by CML typing.     

Refinement of HLA gene mapping with induced B-cell line mutants

The lymphoma cell line BJAB.B95.8.6 was gamma-irradiated to induce mutations of major histocompatibility complex (MHC) encoded genes. Cloned wild-type cells were phenotyped HLA-A1, A2, B 13, 1335, Bw4, Bw6, Cw4, DR5, DRw52, DQwl, DQw3, DPw2, DPw4, GLO1^*1, PGM3^*2-1, and ME1^*0 and possessed two apparently normal chromosome 6s prior to mutagenesis. Loss mutants were selected 5 days after 3 Gy gamma-irradiation employing three complement-fixing monoclonal antibodies specific for HLA-A2 (TÜ101) and Bw4 (TÜ48, TÜ109). Fifteen independently arising mutants were isolated and cloned. Typing with monospecific alloantisera and cell-mediated lympholysis revealed the presence of HLA-A1, 835, Bw6, Cw4, DR5. DRw52, DQw3, and DPw4 specificities on all mutant clones. HLA-A2, B13, and Bw4 were absent. Mutants differed in their expression of class 11 antigens. One group retained DQw1 and DPw2, another was DQw1^–, DPw2⁺, and a third was DQw1^–, DPw2^–. Karyotyping of the wild-type line and selected mutant clones showed that the loss of HLA specificities correlated with deletions which map the HLA-A and -B loci directly to the distal part of the 6p2l.33 region and the class II genes to the region 6p21.33 (proximal) to 6p21.31 (distal) on the short arm of chromosome 6.Abbreviations used in this paper: CML cell-mediated lympholysis - CTX cytotoxicity - DBBA direct bacterial binding assay - EBV Epstein-Barr virus - GLO glyoxalase - IBBA indirect bacterial binding assay - LU lytic units - ME1 cytoplasmic malic enzyme - MHC major histocompatibility complex - MOAB monoclonal antibody - NADP nicotinamide-adenine dinucleotide phosphate - PGM3 phosphoglucomutase isozyme 3 In partial fulfillment of Ph.D. thesis requirements.     

Acute diabetes modulates response to ischemia in isolated rat heart

Role of protein kinase C (PKC) isotypes in the regulation of neutrophil function are not clearly known. In the present study we purified the -PKC and -PKC isotypes from human neutrophil. Both the isotypes are immunoreactive only to their respective antibodies. -PKC was further confirmed by RT-PCR using specific primer. Co-factor requirements for both the kinases were found to be different when DG and ceramide were used as second messenger. Selective substrate specificities were determined for both and -PKC using isotype specific pseudosubstrates viz., [Ser²⁵]PKC [19-31] and [Ser¹¹⁹]PKC[113-130] respectively. Endogenous protein phosphorylation by purified -PKC and -PKC showed their functional differences in neutrophil. -PKC phosphorylated 13, 15, 19, 33, 36, 47, 80 and 92 kDa proteins and -PKC phosphorylated 19, 22, 42, 47, 75 and 87 kDa proteins, only exception was the phosphorylation of 47 kDa protein which had been phosphorylated by both the kinases. Differences in phosphorylation between -PKC and -PKC clearly indicate the selective role for these PKC isotypes in the activation sequences of neutrophil.     

Unique T cell Ia antigen expressed on a hybrid cell line producing antigen-specific augmenting T cell factor

Hybrid cell lines were established by fusion between keyhole limpet hemocyanin(KLH) binding T cells of A/J mice and an AKR T cell tumor line, BW5147. Hybrids were selected for the presence of Ia antigen and KLH-specific augmenting activity of their extracts in the secondary antibody response. The detailed phenotypic and functional analysis of 1 of these clones, FL10, is reported here. The hybrid was positive for both Thy1.1 and Thy1.2 antigens and possessed the Lyt-1+,2-,3- phenotype. Both VH and Ia determinants were detected on their cell surface. The IA locus was mapped in the I-A subregion, but the Ia specificities were serologically distinct from those of B cell Ia antigen. This was demonstrated by the fact that anti-Ia antiserum preabsorbed with B cells could react with the hybrid cells, whereas none of the monoclonal anti-Ia specific for private and public determinations of Iak could. The extract from the cell line specifically augmented the in vitro secondary antibody response against dinitrophenylated KLH, and this activity was removed by absorption with antigen and conventional anti-Ia antisera. The results indicate that the cell line, FL10, carries Ia antigen unique to the T cell, which is associated with the antigen-specific augmenting molecule.     

Identification on I-Ak molecules of a functional site recognized by proliferating T-lymphocytes

The inhibitory capacity of 17 monoclonal antibodies (m.Ab.) specific for the products of the I-A ^k subregion was evaluated in proliferative responses of B10.BR T-lymphocytes to GAT, Keyhole limpet hemocyanin, and ovalbumin. Considered in isolation, each m.Ab. mediated inhibitory effects of comparable magnitude on these three different proliferative responses. On the other hand, clear differences were observed when the magnitude of the inhibitory effects was compared from one m.Ab. to another. The m.Ab. were consequently classified as strong or moderate-to-weak inhibitors of T-cell proliferative responses. Evidence was simultaneously gained indicating the following: (a) the determinants recognized by different m.Ab. were expressed on the same molecules; (b) the differences in affinity of the m.Ab. for I-A^k positive cells did not explain their differences in inhibitory capacities; (c) conversely, the inhibitory capacity of each m.Ab. followed its ability to inhibit the cell surface fixation of Ia.17-specific 10-2.16 m.Ab.; (d) the strong inhibitory capacity of some m.Ab. was not related to a special ability to modulate cell surface Ia molecules. These results suggest that antigen recognition by T lymphocytes is preferentially restricted by a functional site of the I-A^k molecules related to the Ia.17 and Ia.1 specificities.Abbreviations EDTA Ethylenediamine-tetraacetic acid disodium salt - EHAA Eagle's Hanks' amino acids medium - FCS fetal calf serum - in polypeptide G is glutamate, A, alanine, T, tyrosine - HEPES N-2-hydroxy-piperazine-N-2-ethane sulfonic acid - kd dissociation rate constant - KLH Keyhole limpet hemocyanin - LPS lipopolysaccharide - m.Ab. monoclonal antibodies - NP-40 nonidet P-40 - PBS phosphate buffered saline - PBS-BSA PBS supplemented with 1% bovine serum albumin - PBS-BSA-NP-40 PBS-BSA supplemented with 0.5% NP-40 - RT room temperature - SEM standard error of the mean - s.c. spleen cells     

T(Iat)- and B(Iab)-cell alloantigens determined by theH-2 linkedI region in mice

The specificity of an antiserum directed againstI region associated (Ia) antigens is described. The serum was raised in (DBA/1×B10.D2)F₁ mice against lymphocytes of AQR mice, differing from the responder for theI region only. The serum reacts with Ia antigens expressed on B cells (Iab) as well as with Ia antigens expressed on T cells (Iat). Absorption studies indicate that B cells possess at least two Ia antigens, and one of these is shared by T cells. However, this shared antigen is not present on the surface of lymphocytes of thymectomized mice. Analysis of the strain distribution of Iab and Iat antigens revealed that the Iab antigens are present on lymphocytes of mice carrying theIA ^k subregion and that the Iat antigens are present on lymphocytes of mice carryingI region genes of theH-2 ^k haplotype located between theIA andIB subregions. This conclusion is based on the analysis of the antiserum's reactivity with T and B cells of the strains B10.A(2R), B10.A(4R) and B10.HTT: the serum reacts with B and T cells of B10.A(2R) but only with B cells of B10.A(4R) mice and only weakly with T cells of B10.HTT mice.Abbreviations ALG antimouse lymphocyte globulin from rabbits - B cells bone marrow derived lymphocytes - B10 C57BL/10Sn mice - D1D2F₁ (DBA/1×B10.D2)F₁ hybrid mice - GVHR graft-vs-host reaction - Ia I region associated antigen - Iab on B cells - Iat on T cells - MLR mixed lymphocyte reaction - T cells thymus-derived lymphocytes - Thy-1 thymus antigen 1, formerly called theta - Tx-Lyc lymphocytes of thymectomized, ALG treated, lethally irradiated and anti-Thy-1 treated bone marrow reconstituted mice - 2R B10.A(2R)/SgSn mice - 4R B10.A(4R) mice     

The free and the β2-microglobulin-associated heavy chains of HLA-A,B alloantigens share the antigenic determinant recognized by the monoclonal antibody Q1/28

Serological and immunochemical assays have shown that the monoclonal antibody Q1/28 recognizes an antigenic determinant which is expressed on the heavy chain of subsets of HLA-A, B antigens and is distinct from those defining the serological polymorphism of this system. Association of the HLA-A, B heavy chain with ₂-microglobulin is not required for expression of the antigenic determinant recognized by the monoclonal antibody Q1/28, since this antibody can immunoprecipitate a 45 000 m. w. component from radiolabeled lymphoid-cell glycoproteins immunodepleted with either an anti-human ₂-microglobulin xenoantiserum or the MoAb W6/32 to framework determinants of HLA-A, B, C antigens. Furthermore, the MoAb Q1/28 can immunoprecipitate a 45 000 m. w. component from an NP40lysate of radiolabeled Daudi cells, which lack the genetic information for ₂-microglobulin. The determinant recognized by the MoAb Q1/28 is relatively resistant to denaturing treatments and does not appear to be carbohydrate in nature. The MoAb Q1/28 is the first example of an antibody which recognizes an antigenic determinant expressed on both the ₂-microglobulin-associated and free HLA-A, B heavy chains.     

Serological expression after sequential double transfection with purified HLA-11 gene of mouse fibroblasts carrying human beta-2 microglobulin

A genomic cosmid library constructed from DNA from a genotyped individual (JF = HLA-A11, Cw–, B38/A26, Cw7, B51) was screened for clones containing class I histocompatibility genes. Among these clones, one was found to carry a 4.8 kb Hind III fragment which is highly correlated with HLA-A11. This clone was used to transfect LMTK⁺ cultured mouse fibroblast transformants expressing human beta-2 microglobulin. The human beta-2 microglobulin heavy chain-associated determinant was positively detected by the M18 monoclonal antibody. HLA-A11 expression on these doubly transformed cells was specifically demonstrated by complement-dependent cytotoxicity with HLA-A11 + A3-specific but not with HLA-A3-specific monoclonal antibodies. Absorption studies with human alloantisera confirmed the presence on these cells of HLA-A11 determinants and of cross-reacting determinants which absorbed anti-HLA-A1 and –A3 alloantisera. The JF5-J27 transfected cell expressed both heavy and light chains of human class I histocompatibility genes.Abbreviations used in this paper ₂m beta-2 microglobulin - CTL cytolytic T lymphocytes - FCS fetal calf serum - HAT hypoxanthine-azaguanine-thymidine - kb kilobase pair - MHC major histocompatibility complex - MoAb monoclonal antibodies - PBL peripheral blood lymphocytes - PEG polyethylene glycol - r correlation coefficient This study is dedicated to the memory of Jean-Jacques Metzger.     

Immunohistochemical localisation of substances reactive to antisera against α-and β-endorphin and met-enkephalin in the brain of Rana temporaria L.

Summary In the brain of Rana temporaria, two distinct systems reactive with - and -endorphin antisera, respectively, and with a met-enkephalin antiserum, have been detected immunohistochemically.Neurons reacting with - and -endorphin antisera are located (1) in the preoptic nucleus, and (2) in the pars ventralis of the tuber cinereum. Immunoreactive nerve fibres of both groups of perikarya end in the infundibular floor near the capillaries and the preoptico-hypophysial tract. Control reactions have shown that the immunoreactivity is suppressed by the corresponding antigens, but also by -LPH. In view of these results the immunoreactive systems examined correspond to an /-endorphin system or a lipotropinergic system.Neurons reacting with the met-enkephalin antiserum are located in the paraventricular organ. Intense immunofluorescence was observed in the infundibular floor. Controls show that the labelling by met-enkephalin antiserum is exclusively suppressed by met-enkephalin.In the pituitary gland, on the other hand, - and -endorphin antisera reveal: 1) the MSH/ACTH-like cells of the pars intermedia and 2) the ACTH-like cells of the pars distalis.Supported by the D.G.R.S.T., Contrat no 77.7.0648     

Cytotoxic T cell lines recognize autologous and allogeneic melanomas with shared or cross-reactive HLA-A

Summary Cytotoxic T lymphocytes (CTL), CD3⁺, / T-cell-receptor-positive, are important effector cells with specific immunity in melanoma patients. The establishment and expansion in vitro of CTL of a specific phenotype to tumor cells strongly depends on the method of activation and sensitization with tumor cells. We generated CD3⁺ CTL lines to melanoma by co-culturing peripheral blood lymphocytes with autologous irradiated melanoma cells and repetitive stimulation with high-dose interleukin-4 in a cocktail culture medium. CTL lines were investigated for their specificity to kill autologous and allogeneic melanoma. Histocompatibility locus antigen (HLA) class I (A, B) molecules are important restrictive recognition antigens for CTL. Although these antigens are highly polymorphic, they can share a similar immunogenic molecular epitope(s) and can be immunologically cross-reactive. The CTL lines generated were found to kill not only autologous melanoma, but also allogeneic melanomas having class I HLA-A antigens shared or cross-reactive with autologous HLA-A. These CTL lines were poor killers of melanomas bearing non-shared or non-cross-reactive HLA-A. Cold-target inhibition assays demonstrated this CTL cross-reactivity to allogeneic melanoma specificity. Epstein-Barr-virus-transformed autologous and allogeneic B lymphoblastoid cell lines failed to block autologous melanoma killing, indicating that CTL were not recognizing major histocompatibility complex antigens, serum proteins or culture medium products as the primary target antigen. HLA-A2 was the major shared HLA-A antigen recognized by CTL lines on the melanoma lines studied. CTL lines also recognized shared HLA-A11 and A24 on allogeneic melanoma. There were no CTL lines showing restriction to HLA-B. These results suggest that common tumor-associated antigens are present on melanomas and are recognized in association with distinct HLA-A epitopes by CTL.This study was supported by grant CA12 582 awarded by the National Cancer Institute, USA     

Identity of molecules bearing murine ia alloantigenic specificities Ia.7 and Ia.22: Evidence for a single type of I-E molecule in homozygotes

In homozygous mice bearingI regions derived from haplotypek, only a single type of Ia molecule bearing the alloantigenic specificities Ia.7 and Ia.22 was found using techniques of sequential immune precipitation and tryptic peptide analysis. As suggested at the fourth Ir Gene Workshop (Sachs 1978), Ia.7 is considered here to be an antigenic determinant associated with I-E-subregionencoded molecules, i. e., it is excluded from theI–C subregion. TheI–C subregion is currently defined mainly by functional traits. It is now known that the I-E molecules are composed of an chain encoded in theI–E subregion, and a chain encoded in theI–A subregion. Since theI–C subregion is not involved with the determination of these Ia molecules, and since in homozygotes there is apparently only a single type of molecule bearing both specificities Ia.7 and Ia.22, the term I-E/C molecule should probably be dropped in favor of the simpler designation I-E.     

Interaction between des-Tyr1-γ-endorphin and HLA class I molecules: Serological detection of an HLA-A2 subtype

Preincubation of lymphocytes with des-Tyr¹--endorphin (DTE) inhibits the reaction between some HLA alloantisera and their corresponding antigens. One HLA-A2-specific antiserum was found which could detect a subtype of the HLA-A2 antigen on DTE-treated lymphocytes from some donors. Comparison with the HLA-A2 subtypes as defined by a combination of cytotoxic T lymphocyte typing and biochemistry showed a complete correlation with the previously described HLA-A2.3 subtype.     

Cytological localization of α-MSH,ACTH and β-endorphin in the pars intermedia of the cichlid teleost Sarotherodon mossambicus

Summary The pars intermedia of S. mossambicus contains two different endocrine-cell types. The predominant cell type is lead-haematoxyline-positive and assumed to synthesize MSH and related peptides. The second cell type is PAS positive and its function and product(s) are unknown. Staining of light-microscopic and ultrathin sections with antisera against -MSH, ACTH 1–24 and human -endorphin revealed that only the lead-haematoxyline-positive cells of the pars intermedia react with these antisera, and that the secretory granules of these cells contain compounds that were immunoreactive to all three antisera. These findings are in line with the hypothesis that -MSH, ACTH and endorphins are derived from the same precursor molecule. No specific reaction with one of the antisera could be detected in the PAS positive cells.     

Immunoglobulin isoantigens (allotypes) in the mouse

Murine antisera raised against allogeneic lymphoid cells often contain antibodies to IgM allotypes. Rarely, allotypic antibodies to IgM have been found after immunization withB. pertussis anti-B. pertussis conjugates. Using both types of antibodies, we have defined a new constant-region locus for both secreted and membrane-bound chains. This locus,Ig-6, is closely linked to the previously described H-chain constant-region loci (Ig-1 throughIg-5) and is subject to allelic exclusion. We have identified three alleles and four antigenic specificities ofIg-6.Authors listed alphabetically     

Antigen specific T cell factors

Summary Antigen specific helper and suppressor factors have a similar structure, with two major sections, a variable region, determining antigen specificity which is likely to be controlled by Immunoglobulin V_H genes, with which it shares idiotype and framework determinants. Specific factors also have a constant region which does not vary between strains and minimally between species or with the antigenic specificity of the factors, which are defined by rabbit anti-helper or anti-suppressor antisera. This region determines the biological function of the molecule. Anti-Ia antisera react with factors, but the nature and function of la molecules on T cell factors is still unclear. The model of specific factor structure, with C and V regions resembles that of immunoglobulin, and it is thus possible that the C region of factors, like the V region is Ig linked. Because there are multiple T cells, helping and suppressing antibody responses specifically, it seems improbable that all of these cell could interact directly with, rare antigen-specific B cells. Thus we propose that macrophage presenting cells are the key to the integration of signals for immune induction and regulation for T and B cells. Since Ir genes have been identified in the macrophage presenting cells interacting with both T and B cells, this suggests that macrophage Ia antigens are of importance in the integration of triggering signals for the lymphoid pool.