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CD8(+) cytotoxic T lymphocytes (CTL) are key determinants of immunity to intracellular pathogens and neoplastic cells. Recognition of specific antigens in the form of peptide-MHC class I complexes (pMHCI) presented on the target cell surface is mediated by T cell receptor (TCR) engagement. The CD8 coreceptor binds to invariant domains of pMHCI and facilitates antigen recognition. Here, we investigate the biological effects of a Q115E substitution in the alpha2 domain of human leukocyte antigen (HLA)-A*0201 that enhances CD8 binding by approximately 50% without altering TCR/pMHCI interactions. Soluble and cell surface-expressed forms of Q115E HLA-A*0201 exhibit enhanced recognition by CTL without loss of specificity. These CD8-enhanced antigens induce greater CD3 zeta chain phosphorylation in cognate CTL leading to substantial increases in cytokine production, proliferation and priming of naive T cells. This effect provides a fundamental new mechanism with which to enhance cellular immunity to specific T cell antigens.

Original publication

DOI

10.1002/eji.200636765

Type

Journal article

Journal

Eur J Immunol

Publication Date

05/2007

Volume

37

Pages

1323 - 1333

Keywords

Amino Acid Sequence, Antigen Presentation, CD8 Antigens, Epitopes, T-Lymphocyte, HLA-A Antigens, HLA-A2 Antigen, Humans, Lymphocyte Activation, Molecular Sequence Data, Mutation, Protein Structure, Quaternary, Receptors, Antigen, T-Cell, Surface Plasmon Resonance, T-Lymphocytes, Cytotoxic, Transfection