title: Recognition of allo-peptide is governed by novel anchor imposition and limited variations in TCR contact residues.
abstract: Immune specificity of a T cell is determined by the TCR contact residues exposed on the antigenic peptide/MHC complex. Naturally processed, biallelic epitopes from H7 minor histocompatibility (mH) antigen vary in position 7 (p7) from aspartic acid (D) to a glutamic acid (E), which differ by an additional methylene (-CH(2)) in the side chain. Here, we show that this variation generates a strong anti-H7a or anti-H7b cytotoxic T cell responses. Further, the H7 allelic peptides use p6 asparagine as their central anchor residue and amino acid variations in either the canonical p5 or the predicted p6 anchor positions in the antigenic epitope were detrimental for TCR recognition. In addition, introduction of any other amino acids, except asparagine, in the polymorphic p7 significantly abolished the ability of anti-H7b TCR recognition. This demonstrates that only an asparagine with an amine group as a side chain instead of a charged oxygen radical could effectively stimulate the anti-H7b specific T cells. Our findings provide evidence that mH antigen-specific TCRs are highly stringent in recognizing their cognate epitopes.
authors.affiliation: Laboratory of Molecular Immunology, Blood Research Institute, Milwaukee, WI 53226, USA.
authors.forename: Corbett J A
authors.initials: CJ
authors.lastname: Reinbold
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Malarkannan
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites / Q000276:immunology; D002460:Cell Line; D018984:Epitopes, T-Lymphocyte; D014644:Genetic Variation; D051379:Mice; D008807:Mice, Inbred BALB C; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D020125:Mutation, Missense; D010455:Peptides / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity
chemical_list: D018984:Epitopes, T-Lymphocyte; D015778:Minor Histocompatibility Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell