Cross-reactivity among evolutionarily distant major histocompatibility complex class I molecules (HLA-B27 and H-2Kk) revealed by xenoreactive T lymphocytes.
A set of mouse HLA-B27-reactive cytotoxic T lymphocyte clones were found to recognize the HLA-B27 molecule in an H-2-unrestricted manner, i.e. independently of any mouse major histocompatibility complex (MHC) molecule. The reactivity patterns of these clones on HLA-B27 variants (positive only on HLA-B*2702 and HLA-B*2701) allowed the identification of residues N77 and A81 of the HLA-B27 molecule as important for their reactivity. The location of these residues in the peptide-binding groove (specificity pocket F) suggested that the reactivity of the clones is dependent on HLA-B27-bound peptide(s). However, several other class I molecules sharing these residues (N77 and A81) were not recognized, indicating that other residues might also be involved. One of the clones was found to display an interesting cross-reactivity with allogeneic H-2Kk molecules, sharing N77 and A81 with HLA-B*2702. Sequence comparison suggested the involvement of residue H9, located in specificity pocket B of the peptide-binding groove, and revealed some similarity of pockets B in HLA-B27 and H-2Kk. The structural basis of such T cell-mediated MHC cross-reactions across species barriers is discussed.
Frangoulis
B
B
Mouse Immunogenetics, INSERM U93, Paris, France.
Reboul
M
M
Rocca
A
A
Pla
M
M
D000595:Amino Acid Sequence; D000818:Animals; D015478:Antigens, Heterophile / Q000276:immunology*; D002999:Clone Cells; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D015478:Antigens, Heterophile; D006183:H-2 Antigens; D015796:HLA-B27 Antigen; D015395:Histocompatibility Antigens Class I