Allorecognition of DR1 by T Cells from a DR4/DRw13 Responder Mimics Self-Restricted Recognition of Endogenous Peptides

• Published in: Proceedings of the National Academy of Sciences - PNAS 1989-06, Vol.86 (11), p.4190-4194
• Main Authors: Lombardi, G., Sidhu, S., Batchelor, J. R., Lechler, R. I.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analysis of the immune response. Humoral and cellular immunity; Antigens; Biological and medical sciences; Candida albicans - immunology; Cell interactions; Cells, Cultured; Clone Cells; Cross reaction; DNA Replication; Fundamental and applied biological sciences. Psychology; Fundamental immunology; HLA-DR Antigens - genetics; HLA-DR Antigens - immunology; HLA-DR Serological Subtypes; HLA-DR4 Antigen; Humans; Immunobiology; Immunoglobulin Allotypes - immunology; L cells; Lymphocyte Activation; Major histocompatibility complex genes; Mice; Models, Molecular; Molecular Sequence Data; Molecular structure; Molecules; Protein Conformation; T cell antigen receptors; T lymphocytes; T-Lymphocytes - immunology; Transponders
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.11.4190

Coculture of a series of anti-DR1Dw1 alloreactive human T-cell clones with autologous (DR4Dw4/DRw13Dw19) antigen-presenting cells and a series of recall antigens revealed that two of four clones tested proliferated in response to Candida albicans. One was restricted by DR4Dw4 and the other was restricted by DRw13D19. These results provide further evidence that many alloreactive T cells have a primary self-restricted specificity and cross-react on allogeneic major histocompatibility complex products. Structural comparison of the responder and stimulator DR molecules for these clones revealed that the regions predicted to contact the T cells' receptor, and thereby to determine self-restriction, are identical in sequence for DR4Dw4 and DR1Dw1 and differ by one residue between DRw13Dw19 and DR1Dw1. The DRβ residues that differ between responder, DR4Dw4 and DR13Dw19, and stimulator, DR1Dw1, are predicted to contribute to antigen binding. This implies that these anti-DR1 T cells may be specific for endogenous peptides that are bound by DR1 and not by the responder DR products, seen in a self-restricted manner. These T-cell clones also cross-reacted on DR4Dw13 and DRw14Dw16 molecules and on a human/murine hybrid class II dimer DR1β /I-Eα . These reactions are discussed in terms of self-restricted peptide recognition. Thus these data suggest that in certain responder/stimulator combinations allorecognition may resemble self-restricted recognition of fragments of endogenous antigens that are bound by stimulator but not by responder major histocompatibility complex products.