International Immunology, Vol. 12, No. 3, 375-383,
March 2000
© 2000 Japanese Society for Immunology
Minimal peptide length requirements for CD4+ T cell clones—implications for molecular mimicry and T cell survival
1 Cellular Immunology Section, Neuroimmunology Branch, NINDS, National Institutes of Health, Building 10, Room 5B-16, 10 Center Drive, MSC 1400, Bethesda, MD 20892, USA
2 Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, CA 92121, USA
3 Multiple Peptide Systems, 3550 General Atomics Court, San Diego, CA 92121, USA
Correspondence to: R. Martin
CD4+ T lymphocytes usually recognize peptides of 12–16 amino acids in the context of HLA class II molecules. We have recently used synthetic peptide combinatorial libraries to dissect in detail antigen recognition by autoreactive CD4+ T cell clones (TCC). The results of these studies demonstrated that antigen recognition by T cells is highly degenerate and that many cross-reactive ligands can be defined, some of which much more potent than the selecting autoantigen. Based on these observations, we examined the response of a myelin basic protein-specific HLA class II-restricted CD4+ TCC to truncation variants of optimal ligands. Surprisingly, pentapeptides, tetrapeptides and even tripeptides derived from different segments of the optimal ligands were recognized by the TCC, and some were even more potent than the selecting autoantigen. In addition, these peptides enhanced the survival of the TCC at low concentration. The relevance of this finding was supported by the generation of pentapeptide-specific CD4+ TCC from peripheral blood lymphocytes. These observations not only change existing views on the length requirements for activation of CD4+ HLA class II-restricted T cells, but also extend our knowledge about the flexibility of TCR recognition and the potential for cross-reactivity in the immune system.
Keywords: autoimmunity, CD4+ T cells, cross-reactivity, peptide combinatorial libraries, short antigenic peptides
4 Present address: Department of Neurology, Clinical Neuroimmunology Section, Rudolf Bultmann Strasse 8, 35033 Marburg, Germany
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