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Homocysteine-treated cells can be specifically lysed by cytotoxic T lymphocytes (CTL) identifiable in patients with ankylosing spondylitis and reactive arthritis. Sensitization of target cells involves disulfide bonding and the interaction between homocysteine and HLA antigens occurs in a pre-Golgi compartment in the cells. Salmonella-infected B cells are also lysed by homocysteine-specific CTL, suggesting that intracellular invading microorganisms may provide homocysteine which would gain access to the newly synthesized intracellular HLA molecules and modify them inside the cells. Two different mechanisms for homocysteine modification of HLA antigens are proposed: homocysteine could bind directly to the unpaired cysteine residues in HLA antigens, or it could bind indirectly to HLA antigens through cysteine-containing peptides bound to them. Thus, HLA antigens containing unpaired cysteine residues (e.g. HLA B27) could be modified by homocysteine directly or indirectly, while HLA antigens without unpaired cysteine residues (e.g. HLA A68) could only be modified indirectly. The results are discussed in relation to the potential involvement of homocysteine-specific CTL in ankylosing spondylitis and reactive arthritis, both of which are related to bacterial infections, associated with HLA B27, and considered to be autoimmune diseases.

Original publication

DOI

10.1002/eji.1830260707

Type

Journal article

Journal

European journal of immunology

Publication Date

07/1996

Volume

26

Pages

1443 - 1450

Addresses

Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, GB. x.m.gao@ic.ac.uk

Keywords

B-Lymphocytes, T-Lymphocytes, Cytotoxic, Cell Line, Endoplasmic Reticulum, Stem Cells, Humans, Salmonella Infections, Sulfhydryl Compounds, Homocysteine, HLA-B27 Antigen, HLA Antigens, Epitopes, Lymphocyte Count, Immunization, Base Sequence, Kinetics, Molecular Sequence Data, Adult, Middle Aged, Female, Male