Lymphocyte specificity to protein antigens. II. Fine specificity of T-cell activation with cytochrome c and derived peptides as antigenic probes.

Abstract

Murine T-lymphocyte specificity was determined in a system of antigen driven in vitro T-cell proliferation using cytochrome c molecules from different species, their derived peptides and reconstituted hybrid proteins. It was observed that primed T cells could discriminate between peptide fragments which differed from each other at a single amino acid residue. These conclusions were substantiated by the pattern of cross-reactivity noted in the response of closely related cytochrome c proteins as well as when artificial hybrid molecules reconstituted by the covalent linkage of peptide fragments were analyzed. The pattern of specificity observed appeared to be haplotype (BDF1) dependent although similar conclusions about the fine specificity of T cells in the response to cytochrome c have been obtained in other strains but associated with different residues.

Distinct H-2 -linked Ir genes control both antibody and T cell responses to different determinants on the same antigen, myoglobin

“…This approach is feasible for the antibody studies because the fragments are in equilibrium with the native conformation and for the proliferation studies because the native conformation may not be necessary for such T cell responses (5). 19), and lysozyme (20). Also, Mozes et al (21) A logical extension of the present results is that each antigenic determinant on a complex multideterminant antigen is under the control of a distinct Ir gene.t The detection and mapping of an Ir gene requires the existence of a low responder strain.…”

The identification of tyrosine as a common key residue in unrelated H-2Kd restricted antigenic peptides

“…For example, 44% (25 out of 57) of the peptides listed in one study as reported T cell epitopes (32) contain at least one Tyr residue. In this context, it is interesting to recall that the Tyr-containing peptides NP 50-63 and Y(NANP) 3 Fig. 3; unpublished results).…”

“…In many cases, T cell antigens can be mimicked by defined natural or synthetic peptides (3,4). Analysis of the structure of the MHC class I molecule HLA-A2 by X-ray crystallography showed that most of the polymorphic residues are located within a groove formed by two a-helices overlying an eight-strand /3-sheet (5,6).…”

Hapten-reactive inducer T cells. I. Definition of two classes of hapten-specific inducer cells.

“…The repeated failure of antibodies directed against soluble antigen to block T cell proliferation has led to two major hypotheses: (a) B cells and their secreted products, antibodies, recognize epitopes that differ from determinants recognized by inducer T cells (17,18); and (b) antigen processing creates new determinants that are not recognized by antibodies because of structural or conformational changes (9,19,20). We show that antibodies specific for epitopes that are not altered during processing 2 Definition of inducer cells as hapten and conjugate specific refers to specificity of activation rather than specificity of binding.…”