Experimental allergic orchitis in mice

Susceptibility to the induction of murine autoimmune orchitis was found to be associated with the locus controlling Bordetella pertussis-induced sensitivity to the vasoactive amine, histamine. Only those inbred and H-2 congenic strains of mice possessing both the H-2 ^d haplotype and the locus for susceptibility to B. pertussis-induced sensitivity to histamine developed autoimmune orchitis. In addition, segregation analysis of backcross generation mice also demonstrated a high degree of correlation between susceptibility both to disease and to histamine sensitization, which was indicative of additional multigene control. Pertussigen-histamine sensitization factor (P-HSF) was only effective in eliciting disease when it was administered on the same day, or within a period up to 6 days following sensitization with mouse testicular homogenate-emulsified in complete Freund's adjuvant. P-HSF induced sensitivity to histamine was not found to be associated with an increase in the vascular permeability of target tissue. Thus, B. pertussis-induced sensitivity to histamine appears to play a more crucial role during the sensitization phase of autoimmune orchitis induction, rather than at the inflammatory or effector phase of the disease.     

Experimental allergic orchitis in mice

Inbred strains of mice were studied for their susceptibility to the induction of experimental allergic orchitis after sensitization with mouse testicular homogenate in complete Freund's adjuvant accompanied by injections of extract from Bordetella pertussis. Susceptibility to autoimmune orchitis was found to be linked to the major histocompatibility complex in BALB/c and C57BL/10 mice and mapped to genes encoded within the H-2D ^dregion. In five of six groups of bidirectional (susceptible × resistant) F₁ hybrids, H-2D ^d-linked susceptibility was inherited as a dominant autosomal trait. However, in (BALB/cByJ × DBA/2J)F₁ and (DBA/2J × BALB/cByJ)F₁ hybrids, dominant autosomal resistance to the induction of autoimmune orchitis was observed. Backcross analysis between the resistant F₁ hybrid and the susceptible BALB/cByJ parent suggests that a single independently segregating DBA/2J locus is capable of negating H-2D ^d-linked susceptibility, and controls resistance to the induction of autoimmune orchitis.Abbreviations used in this paper BP extract Bordetella pertussis extract - CFA complete Freund's adjuvant - EAO experimental allergic orchitis - Ir immune response - MHC major histocompatibility complex - MLH mouse liver homogenate - MTH mouse testis homogenate - PI pathology index     

Meiotic recombination within the H-2K-H-2D interval: characterization of a panel of congenic mice,including 12 new strains,using DNA markers

Intra-H-2 recombinant congenic strains are widely used to localize traits to specific subregions of the major histocompatibility complex and have provided evidence for the existence of meiotic recombinational hotspots in mammals. Forty-seven intra-H-2 recombinant strains, including 12 not previously reported, have been identified by serological typing in our laboratory. We have extended the analysis of the cross-over sites in these mice using DNA markers for Ab, Aa, Eb, Ea, Cyp21-ps, D17Tu3, Bat7, and Bat5. The recombinant chromosomes of these congenic strains include loci derived from the a, b, f, k, p, q, r, s, u, and v haplotypes of H-2, providing a diverse panel of strains. Although some alleles of Bat7 could not be distinguished from one another, results from the majority of strains indicated a probable gene order of C4Slp/D17Tu3-Bat7-Bat5-H-2D. No recombinants between Cyp21-ps, C4Slp, and D17Tu3 were observed. The crossover sites in 31 of the 47 intra-H-2 recombinants were within the C4Slp/D17Tu3—H-2D interval; of these 31 crossovers, three were bracketed by D17Tu3 and Bat7, ten by Bat7 and Bat5, seven by Bat5 and H-2D, and 11 by D17Tu3 and Bat5. The results from all 47 strains suggest recombinational hotspots within the C4Slp/D17Tu3—H-2D interval and emphasize the influence that specific haplotypes can have on preferred crossover sites. Correspondence to: G. A. Carlson.     

Genetic susceptibility to post-thymectomy autoimmune diseases in mice

The strain distribution pattern of five different post-thymectomy autoimmune diseases was determined in 21 inbred and two congenic, resistant strains of mice. The results indicated that susceptibility genes outside the H-2 complex may be involved in the development of localized autoimmune diseases in neonatally thymectomized mice. Studies of recombinant inbred strains also showed that susceptibility to gastritis was not associated with the H-2 haplotype but appeared to be influenced by a minor histocompatibility locus. Possible linkage to the H-2 complex was suggested only in the development of coagulating gland adenitis. Although one experiment showed that susceptibility to orchitis and coagulating gland adenitis was inherited as a recessive trait, further studies are required to determine the exact mode of inheritance in each disease system.     

H-2 class I loci determine sensitivity to MCMV in macrophages and fibroblasts

Peritoneal (PM) and bone marrow-derived (BMM) macrophages and lung fibroblasts (LF) from inbred, intra-H-2 recombinant, H-2 mutant, and hybrid mice were infected with murine cytomegalovirus (MCMV) under centrifugal enhancement. At the concentration of virus employed, peritoneal macrophages from strains carrying Kd, Kb, D^d, KS and/or D^s, K4 and/or D4 alleles could be infected to a level of 80%–100%, as assessed by viral antigen expression or loss of Fc receptors. Cells lacking these haplotypes and carrying K^k, K^f, D^k, Df, or Db were resistant, yielding levels of infection below 20% . The background (non-H-2) and class II genotype and the S allele did not influence the proportions of cells infected. Furthermore, sensitivity was dominant in the F, progeny of H-2 b x H-2 k and H-2d x H-2 k crosses, and was not compromised by thebm1, bm3, bm10, or bm14 mutations in the al or2 regions of Kb orD ^b. The proportions of cells able to release infectious virus were low, but paralleled the frequencies of viral antigen expression. The class I genotype also determined susceptibility to MCMV infection in BMM and LF, although up to 35% of H-2 k BMM and 46% of H-2 k LF could be infected. The findings are consistent with an association between K and D antigens and a cellular receptor for MCMV on all three cell types.     

Syngeneic sensitization of mouse lymphocytes on monolayers of thyroid epithelial cells: IV. Correlation with H-2 haplotypes

In vitro primary syngeneic sensitization on monolayers of thyroid epithelial cells was performed with 21 inbred strains of mice representing 11 original H-2 haplotypes. Significant differences in the proliferative responses, assessed by thymidine uptake, were found to be related to the major histocompatibility complex haplotype. This result was further confirmed using congenic resistant strains of mice. In comparison with the experimental autoimmune thyroiditis induced by syngeneic thyroglobulin and adjuvant, primary syngeneic sensitization on monolayers of thyroid epithelial cells appeared to be under the same genetic control (H-2^k strains being good responders, while H-2^b mice are poor responders).     

Low H-2 polymorphism in some Israeli wild mouse populations

Two populations of the wild house mouse, Mus domesticus, found living close to each other (one inhabited a chicken coop and the other an open field at the Educational Farm of the Hebrew University of Jerusalem, East Talpiot, Jerusalem) were studied for their H-2 polymorphism. These two populations were selected because they are well characterized in terms of their ecological parameters; they have been under continuous surveillance for several years. Twenty-seven H-2 homozygous lines were produced by mating wild mice from these two populations with laboratory strains. The H-2 ^w homozygotes were then characterized by serological typing with monoclonal and polyclonal antibodies specific for the known allomorphs controlled by the class I H-2K and H-2D loci or the class II H-2A and H-2E loci. They were also used as donors for immunizations and for the selection of antisera defining the H-2 haplotypes carried by these lines. Four new H-2 haplotypes could be identified: H-2 ^w82 (K ^wl6 D^ws2) H-2 ^w83 (K ^w83 D^w16) H-2 ^w84 (K ^w84 D^w84) and H-2 ^w85 (K ^w83D^w84) the last haplotype being a recombinant derived from H-2 ^w83 and H-2 ^w84. Antinsera defining the new haplotypes were then used for a study of the wild populations. This study revealed that the populations contain only the four identified H-2 haplotypes, having three alleles at the H-2K locus (K ^w16 K^w83, K^w84) and three alleles at the H-2D locus (D ^w16, D^w82 and D ^w84). The alleles occur in the populations with a frequency of 0.12–0.54. There were no significant differences in gene frequencies between the two populations, and the allele frequencies remained more or less stable. There was a significant excess of heterozygotes for at least some of the genes, compared with the frequency expected from Hardy-Weinberg equilibrium. The same antisera were also used to type other populations in the vicinity of Jerusalem. In one population, located 30 km west of Jerusalem, the mice failed to react with any of the reagents. In the other two populations, located 15 km west and 40 km northeast of Jerusalem, three of the four H-2 haplotypes found in East Talpiot were present at high frequencies. It appears, therefore, that only three main H-2 haplotypes and two or three minor ones are present in the area around Jerusalem. This study thus provides the first example of a large mainland population in which the H-2 polymorphism is comparable to that of many other non-H-2 loci.     

Genetic analysis of the non-H-2-linked Ir genes controlling the cytotoxic T-cell response to H-Y in H-2 d mice

The T-cell mediated immune responses to the male specific minor histocompatibility antigen H-Y in mice have been studied extensively as a model for immune responses to other weak antigens like tumor antigens or autoantigens. In a recent analysis of the strain distribution of the cytotoxic T-cell (Tc-cell) responsiveness to H-Y, it has been found that genes both within and outside the H-2 complex exert an interactive control. Whereas the H-2 ^b strains all are high responders, independent of their non-H-2 background, other H-2 haplotypes (d, k, and s) only allow for a response if they are combined with certain non-H-2 genes. The H-2-linked immune response genes (Ir-genes) have been previously mapped to the I and K or D region of the H-2 complex, but the mapping of the non-H-2 genes has not yet been established. In this study evidence is presented, using recombinant inbred strains and immunoglobulin heavy chain (Igh) congenic strains of mice, to show that there is more than one non-H-2 Ir-gene involved, that the main controlling genes are not linked to the Igh complex, and that at least one non-H-2 Ir-gene is linked to the H-3 region on chromosome 2. This region includes genes for beta-2-microglobulin (2m), the Ly-mllalloantigen a polymorphic cell surface glycoprotein (Pgp-1), a B-cell specific antigen Ly-4, a transplantation antigen H-3, and genes (Ir-2) controlling the immune response to Ea-1 and H-13.     

H-2-linked genes determine the level of the primary in vitro anti-Mls response

The level of cell proliferation and interleukin-2 (IL-2) production observed in an anti-Mls mixed lymphocyte reaction between spleen cells from H-2 compatible, Mls incompatible mouse strains is determined by the H-2 haplotype of the mouse combination. Thus, while AKR (H-2 ^k) spleen cells stimulated strong M1s^a responses in H-2^k responder cells, AKR H-2b spleen cells stimulated no or negligible M1s^a responses in responder cells from H-2 ^bmouse strains. This effect was observed at the levels of IL-2 production and cell proliferation. The magnitude of the response observed using F₁ (H-2 ^k/H-2 ^b) responder cells was found to be a function of stimulator rather than responder cells. The poor stimulatory capacity of AKRH-2 ^bspleen cells was also shown not to be due to the loss of the stimulatory Mls ^aallele during the construction of the congenic strain from AKR and C57BL/6 parental strains. Using stimulator cells from a second series of congenic mice, we found H-2 ^b(strain DLLP) again to represent a poorly Mls^a stimulatory H-2 haplotype. In addition, H-2^q (DBA/1) cells displayed very poor Mls^a stimulatory potential while H-2^d (D1.C) cells were efficient Mls^a stimulators. Again the effect was shown to be at the level of the stimulator cells. In toto, our findings indicate that the H-2 ^kand H-2 ^dhaplotypes encode strong Mls^a stimulatory potential while the H-2 ^band H-2 ^qhaplotypes determine poor Mls^a stimulatory potential in primary in vitro responses, measured as cell proliferation and IL-2 production.Abbreviations used in this paper: CTL cytotoxic T lymphocyte - IL-1 interleukin-1 - IL-2 interleukin-2 - MLR mixed lymphocyte reaction - NMS normal mouse serum     

A new H-2.1-PositiveD region allele,D dx,controlling two molecules,H-2Ddx and H-2Ldx

The inbred strains GRS/A and LIS/A carry the haplotypeH-2 ^dx , which had earlier been shown to have theK ^d ,I ^f ,S ^f , andG ^f alleles and a previously unknownD region allele,D ^dx . We show here that theD ^dx allele determines a new private specificity, H-2.63, is H-2.28 negative, and determines at least one public specificity of the H-2.1 family. It is thus a second example (afterD ^k ) of a H-2.1-positive H-2.28-negativeD region allele. Capping experiments show that the D^dx product comprises two molecules: H-2D^dx bearing the private specificity H-2.63, and H-2L^dx, which is H-2.63-negative but reacts with sera against the H-2.1 family of specificities. SDS gel electrophoresis of detergent-solubilized immunoprecipitated D^dx products shows that the H-2L^dx antigen has a molecular weight of approximately 45,000 daltons and is associated with a smaller polypeptide (mol. wt. 12,000).     

H-2-linked recessiveIr gene regulation of high antibody responsiveness to TNP hapten conjugated to autogenous albumin

The antibody response to the hapten 2,4,6-trinitrophenyl (TNP) conjugated to autogenous mouse serum albumin (MSA) is regulated by anIr gene(s) located within the major histocompatibility complex (MHC). Both the qualitative and quantitative ability of congenic strains to produce TNP-specific antibodies are functions of theH-2 haplotype. Thus, mouse strains may be classified as high (H-2 ^d), intermediate (H-2 ^b,H-2 ^s), and low responders (H-2 ^a,H-2 ^k,H-2 ⁿ,H-2 ^p,H-2 ^q). Antibody responses, as measured by antigen-binding capacities in modified Farr assays, were compared among strains carrying recombinantH-2 haplotypes and their hybrid progenies. Distinct high- and low-responder phenotypes were evident throughout the time course of both primary and secondary antibody responses. The gene locus controlling specific responsiveness to TNP-MSA, now designatedIr-6, was mapped within theI-B subregion of theH-2 complex. Recessive inheritance of high responsiveness was confirmed in hybrid progenies of three different low × high-responder crosses.     

Glucocorticoid-Induced Cleft Palate in the Mouse: Two Major Histocompatibility Complex, H-2, Loci with Different Mechanisms

Isolated cleft palate is induced in the progeny of pregnant mice that are given glucocorticoids. The incidence varies among inbred strains and with dose and stage of gestation when the drug is given. One chromosomal region responsible for strain-associated differences in sensitivity is the major histocompatibility complex, H-2. H-2^a is associated with susceptibility, H-2^b with resistance. There appear to be both maternal and embryonic genetic factors affecting the sensitivity to glucocorticoids. In experiments reported here congenic strains of mice with H-2^a, H-2^d and H-2^k haplotypes on a C57BL/10 genomic background were used. This allowed the determination of the effect on sensitivity by two H-2 subregions; the subregions are H-2K to I-E and I-C to H-2D. Methods included dose-response analysis and reciprocal cross analysis using dexamethasone given on day 12 of pregnancy. Results show that each subregion affects the strain's sensitivity to dexamethasone-induced cleft palate. The regression coefficients for B10.A-H-2^a (45.4 ± 4.13) were different from those for B10.BR-H-2^k (67.2 ± 10.8) and B10.D2-H-2^d (70.5 ± 9.74). The estimated mean arcsine% cleft palate at 160 mg/kg was different for each strain: B10.A- H-2^a, 53.1 ± 2.19; B10.BR-H-2^k, 33.1 ± 2.27; B10.D2-H-2^d, 25.0 ± 2.75. Different patterns of change in sensitivity were observed among the reciprocal crosses. In summary, the H-2K to I-E subregion seemed to influence both maternal and embryonic factors, whereas only embryonic factors were influenced by the I-C to H-2D subregion. These data suggest that the mechanisms affecting glucocorticoid sensitivity which are genetically encoded within each H-2 subregion are different, and there is an interaction between the alleles. The mode of interaction can be either complementation or epistasis.     

Proximity of the Mep-1 Gene to H-2D on chromosome 17 in mice

The Mep-1 gene on chromosome 17 in mice controls the activity of meprin, a kidney brush border metalloendopeptidase. Most inbred mouse strains of the k haplotype (e.g., CBA, C3H, AKR) are markedly deficient in meprin activity; these mice carry the Mep-1 ^ballele. Mouse strains in which meprin activity levels are normal are designated Mep-1 ^a Studies using congenic and recombinant strains mapped the Mep-1 gene telomeric to H-2D near the Tla gene. To further study the relationship between the major histocompatibility complex and Mep-1, a linkage study was conducted. Mep-1 ^a F₁ hybrids [C3H.A (K ^k D ^d ) × C3H.OH (K ^d D ^k )] were backcrossed with Mep-1 ^b C3H.OH (K ^d D ^k ) parents. The progeny were assayed for H-2D markers, Pgk-2 isozymes, and meprin activity. Recombination between H-2D and Mep-1 occurred in 6 out of 284 mice, a crossover frequency of 2.1%. Mep-1 is therefore 2.1 crossover units telomeric to H-2D and approximately 0.6 crossover units from Tla. The Mep-1 locus provides a new genetic marker for the future mapping of this important area of the mouse genome.     

Expression of HLA-B27 in transgenic mice is controlled by gene(s) mapping between H-2D and H-2L loci

The level of HLA-B27 transgene expression on the cell surface is dependent on the host H-2 haplotype. Mice homozygous for the H-2 ^b , H-2 ^f , H-2 ^f , H-2 ^p , H-2 ^r , and H-2 ^k haplotypes express B27 at high levels. An intermediate level of B27 expression is observed in H-2 ^v mice whereas low levels of B27 are expressed in H-2 ^q and H-2 ^d mice. The decreased expression of B27 maps to the D region of the major histocompatibility complex. Recombinant strain B10.RKDB (D^dL^b) mapped the low expression gene centromeric to H-2L. In order to determine the low expression within the H-2D region, the B27 transgene was introduced into B10.D2-H-2 ^dm1 and BALB/c-H-2 ^dm2 mice. Expression of B27 in both of these strains was high indicating that neither H-2D ^d nor H-2L ^d is responsible for the low expression. This maps the effect between the H-2D and H-2L loci. In addition, introduction of human ₂-microglobulin (₂m) into B10.D2-B27 transgenic mice caused a marked enhancement of B27 expression on the cell surface suggesting that the defect in B27 expression in certain haplotypes is due to an inability of B27 to associate with endogenous mouse ₂m. We propose that gene(s) mapping between D and L (either D2, D3, D4, or some as yet unidentified gene) may be involved in class I assembly by helping association of ₂m with class I. This putative molecule, designated Assembly Enhancer (AE) might have a negative influence in the association between human class II and mouse ₂m.     

Non-H-2 and H-2-Linked immune response genes control the cytotoxic T-cell response to H-Y

The immunoregulation of cytotoxic T-cell responses to the male-specific antigen H-Y in mice has been found to be genetically controlled by genes of the major histocompatibility complex (H-2). Responsiveness was mainly confined to H-2 ^b strains, but it has also been found in recombinant strains, F₁ hybrids, and chimeras that carry at least part of the H-2 ^b haplotype. By using a different immunization procedure it has been shown recently that an H-2 ^k mouse strain (CBA) is also able to mount an equivalent H-Y-specific response. We investigate here, by applying this immunization technique, the responsiveness of other H-2 ^k strains and of strains of other independent H-2 haplotypes. Both responders and nonresponders are found in three haplotypes: k, s, and d. The strain distribution pattern of responsiveness shows a combined influence of non-H-2 and H-2 genes. In certain strains there is a high variability in responsiveness between genetically indentical individual animals. We discuss a model of immune response (Ir) gene function which could account for these observations.     

Serological and complementation studies in four C57BL/6H-2 mutants

C57BL/6 (H-2 ^b ) mice, and four mutants (B6.C-H-2 ^ba , B6-H-2 ^bg1 , B6-H-2 ^bg2 , B6-H-2 ^bh ) derived from this strain after separate mutations had occurred at the same locus within theH-2 complex, were analyzed to determine whether the mutations had led to anyH-2 (or Ia) difference which could be detected serologically. The strains were typed directly with antisera specific for H-2K and H-2D public and private specificities and for the Ia specificities; quantitative absorption studies were also performed for the relevant H-2K^b, H-2D^d and Ia^b specificities. In no case was any quantitative or qualitative difference detected serologically between any of the strains. In addition, by using a variety of techniques to produce and assay for antibody, we failed to produce any antisera between the parental strains and the four mutants. TheH-2 mutations therefore appear to give rise to a type of antigenic specificity which is recognized byT cells and which generateT, but notB cell responses; nor are they recognized by H-2 or Ia alloantisera. The location of the mutating locus within theH-2 complex was shown by the complementation method to be within theK orIA region and not in theIB region, since crosses of the mutant strains with B10.A(4R) or D2.GD failed to complement for a subsequent C57BL/6 skin graft.     

Regulation of Qa-1 expression and determinant modification by an H-2D-linked gene,Qdm

We examined the regulation of cell surface expression of the Qa-1 alloantigens using a panel of monoclonal anti-Qa-1 cytotoxic T-lymphocyte (mCTL) lines. In contrast to previous reports of tissue-specific expression, we found that Qa-1 was widely expressed, resembling the prototypical class I H-2K/D molecules. We further found that an H-2D-linked gene, which we termed Qdm for Qa-1 determinant modifier, controlled expression of certain CTL-defined Qa-1 antigenic determinants. H-2D ^khomozygous haplotypes expressed a recessive allele of the modifier, Qdm ^k, whereas all other H-2 haplotypes tested expressed a dominant allele, Qdm ⁺. The Qdm ⁺ allele regulated in trans Qa-1 epitope expression from a Qdm ^kchromosome, modifying expression of particular CTL-defined Qa-1 antigenic determinants rather than affecting levels of cell surface expression. Mechanisms of Qdm function may include either a novel protein modification system or an unprecedented case of antigen recognition restricted by a nonclassical major histocompatibility complex molecule.     

Corticosteroid-induced cleft palate in mice and H-2 haplotype: Maternal and embryonic effects

This report confirms and expands on the original preliminary observations made by Bonner and Slavkin that corticosteroid-induced cleft palate in mice is associated with H-2 haplotype. Using three congenic strains, B10, B10.A, and B10.D2, our studies demonstrate that B10.A (H-2 ^b) is most susceptible and B10.D2 (H-2 ^d) is least susceptible, B10 (H-2 ^b) being intermediate. Variation in fetal loss among strains accounts for less than 1 percent of the variation in cleft-palate frequency among strains; variation in H-2 haplotype, however, accounts for more than 60 percent of the variation in cleft-palate frequency. With regard to all possible reciprocal F₁ hybrids, our results indicate that while there is a significant maternal effect, maternal haplotype can account for only 11 percent of the variation in cleft-palate frequency among crosses. Embryonic haplotype accounts for 17 percent of the variation, which is indicative of an important embryonic effect. Finally, our studies suggest that susceptibility to corticosteroid-induced cleft palate is associated with the K end of the H-2 complex.     

The histocompatibility-2 system in wild mice

The I-region gene products of 29 wild-derivedH-2 haplotypes on a B10 background (B10.W congenic lines) were typed with alloantisera which detect 17 inbred I-region antigens. Five new I-region antigens were defined by expanding the inbred line panel ofH-2 haplotypes to includeH-2 ^u , H-2^v, andH-2 ^j . Based on serological analyses of the inbred and B10.W lines, the polymorphism of theIA gene (or genes) is estimated to be at a minimum of 15 alleles and theIE gene (or genes) at a minimum of 4 alleles. These results indicate that theIA subregion is more polymorphic than theIE subregion. By combining the I-region typing data with theH-2K andH-2D region typing data reported previously, a total of 11 new natural recombinants of inbredH-2 alleles were detected among the B10.W lines.     

Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells

Mice of the C3H/He and A non-H-2 backgrounds are disparate from mice of the B10 background for the tissue-restricted, non-H-2 alloantigen of epidermal cells (EC), Epa-1, that is expressed by EC but not by lymphocytes (LC), as well as for a number of other alloantigens of the B10 background that are expressed by both EC and LC, generically referred to as lymphocyte/epidermal alloantigens (LEA). In this study, we compared the ability of various H-2 congenic strains on the C3H or A backgrounds to mount cytotoxic T-lymphocyte (CTL) responses to EC from H-2 compatible mice of the B10 background. High responses to Epa-1 were detected only in the H-2 ^aand H-2 ^khaplotypes; H-2 ^b, H-2 ^o1, H-2 ^s, H-2 ^t1, and H-2 ^t2 haplotypes were nonresponders to Epa-1. High responses to LEA were detected in H-2 ^a, H-2 ^b, H-2 ^s, H-2 ^t1, and H-2 ^t2 haplotypes; H-2 ^kand H-2 ^o1 were nonresponsive to LEA. Analysis of the H-2K, I and D region alleles of responders indicates that H-2K ^kis essential for anti-Epa CTL responses, whereas D ^d, D ^b, or K ^swere all permissive for strong anti-LEA responses. The ability to mount a given CTL response was not associated with differences in I-region alleles. These results are discussed in terms of K/D region products serving as Ir-gene products for CTL and in determining the apparent tissue-specificity of CTL.