SV40 T antigen acts as a minor histocompatibility antigen of SV40 T antigen tolerant transgenic mice

The ability of normal mice to mount an SV40 T antigen-specific cytolytic T lymphocytes response when immunized in vivo with splenocytes from the SV40 T antigen transgenic 427-line mice and restimulated in vitro with SV40-transformed fibroblasts, or when immunized with SV40 and restimulated with 427-line splenocytes, was analyzed. Both immunization schemes resulted in an SV40 T antigen-specific immune response, indicating the presence of SV40 T antigen-positive cells in the spleens of these transgenic mice. Normal mice engrafted with skin from 427 donors showed no rejection of the graft. Thus, SV40 T antigen in transgenic 427-line mice is expressed on an undefined cell type in the spleen and acts as a tissue-specific minor histocompatibility antigen.     

The HML-1 antigen of intestinal lymphocytes is an activation antigen.

The Ag recognized by the mAb HML-1 is expressed on more than 90% of human intestinal intraepithelial lymphocytes, whereas in other lymphoid tissues it is rarely or not expressed. In the present study, we have investigated the percentage of HML-1-positive cells in the human intestinal lamina propria and the coexpression of HML-1 with different T cell subset markers. In addition, we studied the inducibility of HML-1 on PBL which normally are HML-1-negative. Flow cytometric analysis of isolated intestinal lamina propria lymphocytes (LPL) showed that about 40% of the cells expressed HML-1, the majority belonging to the CD8-positive subpopulation. Virtually all LPL expressed CD45RO, whereas the percentage of CD29-positive cells was only about 50%, similar to PBL. There were only few cells expressing CD45RA or Leu-8 in the lamina propria. HML-1-positive cells were almost exclusively CD45RA-negative, but were found in both the CD29-positive and the CD29-negative subpopulation of LPL. In vitro stimulation of PBL showed that the expression of HML-1 was inducible on T cells by mitogens, phorbolester, Ag, and rIL-2. Expression of HML-1 was induced with a different time course and with differences in the response to the investigated stimuli compared with CD25. Activated HML-1-positive PBL were also predominantly CD45RA-negative. The findings show that HML-1 is an Ag, which is expressed in vivo on a specific subset of previously activated T cells in the unique environment of the intestinal mucosa, and which can be induced in vitro by different activation signals on PBL.     

Acquired B antigen]

Many cases of acquired B antigens, always observed in group A subjects have been so far reported. Most of them were found in patients with digestive tract disease, essentially colonic cancer. An investigation on 200 patients in a gastroenterology department showed that this B-like antigen was quite frequent (10,6%); it occurred only in A1 individuals and was related to infectious syndrome. Immunological and serological studies of many cases had shown that this B-like antigen differs from that of normal B cells. Groupe A1 cells transfused to patients acquired B activity; on the contrary group A2 and O cells remained unchanged. Likewise, only A1 cell became active when incubated in vitro with C. Tertium A., known to contain a deacetylase. In 1970, we postulated that a deacetylase enzyme could be responsible for this B-like antigen: this enzyme could transform the N-acetylgalactosamine (A specific sugar) into galactosamine, which could cross react with anti-B sera. The relationship between the acquired B antigen and a deacetylase was recently confirmed: A1 acquired B cells, chemically acetylated lost their B reactivity and enhanced their A1 activity. A polyagglutinability, different from that associated with T, Tn, Cad, Hempas has been always found in acquired B cells; nervertheless, because of its weakness, it could sometimes be unnoticed. Besides, it disappeared prior to B reactivity in case of recovery. Like acquired B activity, it decreased in low pH medium of after acetylation of the cells. Nevertheless, this polyagglutinability appears, contrarly to acquired B antigen, in vitro, on all the cells, irrespective of their ABO phenotypes. A deacetylation of N-acetyl-neruaminic acid could explain such a phenomenon.     

The relationship between antigen concentration, antigen internalization, and antigenic complexes: modeling insights into antigen processing and presentation

Native antigen is processed and subsequently presented on the surface of antigen-presenting cells, an important step in the elicitation of an immune response. The early events of antigen processing and presentation include: ingestion of a native antigen, intracellular degradation to expose an antigenic peptide fragment, binding of this fragment with an MHC class II molecule, and display of this newly formed complex on the cell surface. Through the development of a mathematical model, a set of mathematical equations which describes the time-dependent appearance, disappearance, and movement of individual molecules, quantitative insight can be gained into the pathways and rate-limiting steps of antigen presentation. The credibility of the model has been verified by comparison to literature data. For example, it has been shown experimentally that macrophages require 60 min for effective antigen presentation, whereas B cells require 6-8 h. The mathematical model predicts these presentation times and identifies the difference in the cell's respective pinocytic rates and sizes as important parameters. B cells capture antigen in their environment through nonspecific fluid-phase pinocytosis as well as by binding antigen to their surface immunoglobulin, allowing receptor-mediated uptake. Uptake of antigen via receptor-mediated endocytosis has been reported to require 1,000-fold less antigen than uptake via nonspecific pinocytosis. The mathematical model clearly predicts this decrease in concentration. The model also makes quantitative predictions for the number of MHC class II-antigen complexes needed to produce T cell stimulation.     

Poliovirus antigen chimeras.

Poliovirus, the aetiological agent of paralytic poliomyelitis, is arguably the best characterized of all animal viruses. Using recombinant-DNA technology, this information, together with the availability of infectious cDNA clones of the notably safe and efficacious live attenuated Sabin 1 vaccine strains of poliovirus, has enabled the creation of hybrid viruses (chimeras) possessing novel antigenicity. The potential applications of these 'epitope-presentation systems' include their use as immunogens, as antigens for serodiagnosis, and as vaccines.