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 antigenspecific TCRs are highly stringent in recognizing their cognate epitopes.

Mapping the human T cell repertoire to recurrent driver mutations in MYD88 and EZH2 in lymphoma

“…Moreover, T cells can detect even single amino acid changes in proteins. 6 Activated T cells are able to kill target cells presenting their cognate epitope, regardless of protein structure or function. Finally, the adaptive immune system provides immunological memory, which may prevent recurrence of tumors expressing the same mutant proteins.…”

H60: A Unique Murine Hematopoietic Cell-Restricted Minor Histocompatibility Antigen for Graft-versus-Leukemia Effect

“…Many of mouse MiHAs were identified at the molecular level in the late 1990s and early 2000s (8). Of these, MiHAs for which the specific T cell responses have been functionally evaluated are listed in Table 1 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Although MiHAs are short peptides processed from various proteins, the molecular functions of the native proteins are in general irrelevant to their ability to generate allo-responses.…”