Preferential binding of unusually long peptides to MHC class I and its influence on the selection of target peptides for T cell recognition

• Published in: Molecular immunology 2008-03, Vol.45 (6), p.1818-1824
• Main Authors: Burrows, Jacqueline M., Bell, Melissa J., Brennan, Rebekah, Miles, John J., Khanna, Rajiv, Burrows, Scott R.
• Format: Article
• Language: English
• Subjects: Antigen Presentation; Antigen presentation/processing; Cell Line; CTL; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; HLA-B35 Antigen - immunology; Human; Humans; MHC class I; Peptides - immunology; Protein Binding; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; Viral
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2007.09.026

A classic feature of antigen presentation for CD8 + T cell recognition is that MHC class I molecules generally present peptides of 8–10 amino acids in length. However, recent studies have demonstrated that peptides of >10 residues play a significant role in immune surveillance by T cells restricted by some HLA class I alleles. In the present study, we describe several examples of unusually long viral peptides of 11 or 12 residues, recognized by CTLs in the context of HLA-B35. Interestingly, all these immunogenic peptides completely encompass shorter canonical length sequences that conform to the HLA-B35 binding motif, but which fail to stimulate detectable T cell responses. The mechanism for this phenomenon appears to involve the preferential binding to HLA-B35 of the atypically long CD8 + T cell target peptides over the overlapping canonical length sequences. These data suggest that the peptide length specificity of some HLA class I alleles is broad, allowing peptides of >10 residues to sometimes dominate over canonical length class I ligands as targets for T cell recognition.