Cross-reactivity among evolutionarily distant major histocompatibility complex class I molecules (HLA-B27 and H-2Kk) revealed by xenoreactive T lymphocytes

• Published in: European journal of immunology Vol. 23; no. 2; p. 338
• Main Authors: Frangoulis, B, Reboul, M, Rocca, A, Pla, M
• Format: Journal Article
• Language: English
• Published: Germany 01.02.1993
• Subjects: Amino Acid Sequence; Animals; Antigens, Heterophile - immunology; Clone Cells; Cross Reactions; Cytotoxicity, Immunologic - immunology; H-2 Antigens - immunology; Histocompatibility Antigens Class I - immunology; HLA-B27 Antigen - immunology; Mice; Mice, Inbred C3H; Mice, Transgenic; Molecular Sequence Data; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830230206

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.