Structural features of an antigen required for cellular interactions and for T cell activation in a MHC-restricted response.
The protein Ag, tobacco mosaic virus protein, (TMVP) and its tryptic peptide number 8 (residues 93-112 of the protein) exhibit cross-reactivity on the T cell level in some strains of mice (e.g., C3H.SW, C57BL/10); these strains are termed cross-reactive (CR). In other strains such as A/J or B10.BR, no cross-reactivity is exhibited; these strains are termed non-cross-reactive (NCR). Genetic experiments indicated that the cross-reactivity is dominant and that it is mapped to the I-A or I-E region of the MHC, with cross-reactivity exhibited by the I-Ab haplotype but not by I-Ak or I-Ek. Cell reconstitution experiments have indicated that the non-cross-reactivity is associated with the inability of the NCR APC to present Ag. Analysis of the area(s) on peptide 8 which serve(s) as epitope revealed that both strains recognize an overlapping area consisting of 11 amino acid residues in the middle of peptide 8 (residues 97-107), which by itself is nonstimulatory to TMVP- or peptide 8-immune T cells of the CR or the NCR strains. However, the addition of a few amino acid residues of the sequence of peptide 8 to this area converts it to a complete stimulatory epitope. Additivity experiments revealed that the CR strain contains two major T cell populations each recognizing this middle region of peptide 8 when elongated by a few amino acids N-terminally and C-terminally, respectively. In contrast, the NCR strain contains one major T cell population recognizing elongation only N-terminally. Because TMVP (but not peptide 8) requires processing before presentation to T cells, it is postulated that, during processing of TMVP, there occur alterations in the area of the proximal three or four N-terminal amino acids of the region consisting of peptide 8, destroying the only region containing the T cell epitope recognized by the NCR strain, hence TMVP and peptide 8 do not exhibit cross-reactivity in this strain. The same alterations of TMVP still leave intact an epitope consisting of amino acid residues C-terminal to the altered area which is recognized by the CR strain, hence the cross-reactivity exhibited by this strain. The results suggest that the difference in cross-reactivity on the T cell level between TMVP and peptide 8 exhibited by the strains may be due to differences in the orientation of presentation and the subsequent cell recognition of an epitope contained within peptide 8.(ABSTRACT TRUNCATED AT 400 WORDS)
Langton
B C
BC
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis 95616.
Mackewicz
C E
CE
Wan
A M
AM
Andria
M L
ML
Benjamini
E
E
D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins; D002450:Cell Communication; D003429:Cross Reactions; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D014027:Tobacco Mosaic Virus / Q000276:immunology* / Q000502:physiology; D014764:Viral Proteins / Q000276:immunology* / Q000502:physiology
D036022:Capsid Proteins; C009496:H protein, Tobacco mosaic virus; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D014764:Viral Proteins