Abstract
We have generated an alloreactive proliferative T cell clone that only is stimulated by HLA-DPw3+ antigen presenting cells (APC) that at the same time carry HLA-A1. The T cell clone is CD4+, and the proliferation is blocked by anti-DP monoclonal antibodies and not by antibodies towards other class II or towards class I molecules. Family studies show that APC with A1 and DPw3 on different haplotypes (trans) are able to stimulate the clone, and an HLA recombinant family gives evidence that the class I-carrying part of the haplotype is necessary for stimulation to occur. Stimulation is also observed with mixtures of APC expressing DPw3 and APC expressing A1, and likewise, DPw3+ APC become stimulatory when preincubated with supernatants from A1-positive cells. Our studies suggest that major histocompatibility complex (MHC) class I peptides presented by class II are allostimulatory and that APC can process MHC molecules that presumably are presented as allele-specific peptides in the context of other MHC molecules. We hypothesize that presentation of MHC peptides by MHC molecules constitutes an important part of alloreactive phenomena in vivo and in vitro.
Full Text
The Full Text of this article is available as a PDF (408.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baumgartener L., Olson C., Onuma M. Effect of pasteurization and heat treatment on bovine leukemia virus. J Am Vet Med Assoc. 1976 Dec 1;169(11):1189–1191. [PubMed] [Google Scholar]
- Beck B. N., Frelinger J. G., Shigeta M., Infante A. J., Cummings D., Hämmerling G., Fathman C. G. T cell clones specific for hybrid I-A molecules. Discrimination with monoclonal anti-I-Ak antibodies. J Exp Med. 1982 Oct 1;156(4):1186–1194. doi: 10.1084/jem.156.4.1186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
- Brown J. H., Jardetzky T., Saper M. A., Samraoui B., Bjorkman P. J., Wiley D. C. A hypothetical model of the foreign antigen binding site of class II histocompatibility molecules. Nature. 1988 Apr 28;332(6167):845–850. doi: 10.1038/332845a0. [DOI] [PubMed] [Google Scholar]
- Charron D. J., Lotteau V., Turmel P. Hybrid HLA-DC antigens provide molecular evidence for gene trans-complementation. Nature. 1984 Nov 8;312(5990):157–159. doi: 10.1038/312157a0. [DOI] [PubMed] [Google Scholar]
- Eckels D. D., Gorski J., Rothbard J., Lamb J. R. Peptide-mediated modulation of T-cell allorecognition. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8191–8195. doi: 10.1073/pnas.85.21.8191. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gomard E., Hénin Y., Sterkers G., Masset M., Fauchet R., Lévy J. P. An influenza A virus-specific and HLA-DRw8-restricted T cell clone cross-reacting with a transcomplementation product of the HLA-DR2 and DR4 haplotypes. J Immunol. 1986 Jun 1;136(11):3961–3967. [PubMed] [Google Scholar]
- Heath W. R., Hurd M. E., Carbone F. R., Sherman L. A. Peptide-dependent recognition of H-2Kb by alloreactive cytotoxic T lymphocytes. Nature. 1989 Oct 26;341(6244):749–752. doi: 10.1038/341749a0. [DOI] [PubMed] [Google Scholar]
- Heath W. R., Vitiello A., Sherman L. A. Mapping of epitopes recognized by alloreactive cytotoxic T lymphocytes using inhibition by MHC peptides. J Immunol. 1989 Sep 1;143(5):1441–1446. [PubMed] [Google Scholar]
- Janeway C. A. Autoimmune disease: immunotherapy by peptides? Nature. 1989 Oct 12;341(6242):482–483. doi: 10.1038/341482a0. [DOI] [PubMed] [Google Scholar]
- Magli M. C., Abad M. J., Balbas O., Layrisse Z. A T cell clone defining a common DP/DR determinant in strong linkage disequilibrium with HLA-A9. Tissue Antigens. 1988 Nov;32(5):259–266. doi: 10.1111/j.1399-0039.1988.tb01665.x. [DOI] [PubMed] [Google Scholar]
- Maryanski J. L., Pala P., Cerottini J. C., Corradin G. Synthetic peptides as antigens and competitors in recognition by H-2-restricted cytolytic T cells specific for HLA. J Exp Med. 1988 Apr 1;167(4):1391–1405. doi: 10.1084/jem.167.4.1391. [DOI] [PMC free article] [PubMed] [Google Scholar]