Lawrence Steinman, MD

Publication Details

  • POLYMORPHIC RESIDUES ON THE I-A-BETA CHAIN MODULATE THE STIMULATION OF T-CELL CLONES SPECIFIC FOR THE N-TERMINAL PEPTIDE OF THE AUTO-ANTIGEN MYELIN BASIC-PROTEIN JOURNAL OF IMMUNOLOGY Davis, C. B., Mitchell, D. J., Wraith, D. C., Todd, J. A., Zamvil, S. S., McDevitt, H. O., Steinman, L., Jones, P. P. 1989; 143 (7): 2083-2093

    Abstract:

    The effect of polymorphic residues on the A alpha A beta molecule on T cell recognition of the N-terminal nonapeptide of myelin basic protein (R1-9) was determined. Ak-restricted T cell clones recognizing R1-9 were isolated. The peptide-Ia specificities of these clones were determined by testing the response to 1) a panel of peptide analogs of R1-11, 2) splenic APC from mice expressing MHC molecules from serologically distinct haplotypes, and 3) L cell transfectants expressing mutant/recombinant A beta cDNA containing combinations of polymorphic nucleotide sequences from the k and u alleles. Comparisons were made between the Ak-restricted clones and a previously characterized panel of Au-restricted clones. Certain Ak-restricted clones were able to recognize MBP peptide analogs that were not recognized by any of the Au-restricted clones. The Au-restricted T cell clones did not cross-react with R1-9 presented in the context of Ak, whereas the majority of the Ak-restricted clones responded to R1-9 presented in the context of Au. This nonreciprocal cross-reactivity was also reflected in the relative responses of the two sets of T cell clones to the interchange of u- and k-derived residues in the A beta chain. Residues in regions corresponding both the alpha-helical or beta-sheet portions of the hypothetical Ia three-dimensional structure were involved. The results suggest that overall specificity of the T cell clones is the summation of numerous distinct subspecificities for different regions of the peptide-Ia ligand. These results indicate that there can be striking differences in T cell specificity for an autoantigenic epitope, even in the context of A alpha A beta molecules from very closely related haplotypes.

    View details for Web of Science ID A1989AR48600001

    View details for PubMedID 2476496

Stanford Medicine Resources:

Footer Links: