Cooperation or sabotage? Self-peptide–MHC complexes influence T-cell responses to antigens

Abstract

In their Opinion, Ge et al. [1] reviewed some recent published data on the role of self-peptide–MHC complexes in the modulation of immune responses to antigens. The authors suggest that some ‘inconsistencies’ in published findings could be attributed to potential aberrant expression of unusual MHC class II molecules (composed of Aβ and Eα chains) in MHC class II-deficient mice used by Bhandoola et al. [2]. Without debating whether the unusual MHC class II molecules were indeed expressed in the mice used in this particular study, we would like to point out that even aberrant MHC class II expression would not explain all ‘inconsistent findings’ in the field. Depending on the experimental model used, self-peptide–MHC complexes enhance [3], reduce [2,4,5] or exert no influence [6] on the responsiveness of T cells to cognate antigen. It is striking that distinct effects of self-peptide–MHC complexes were observed even when identical T-cell receptor (TCR) transgenic mice were used [3,5]. Thus, neither aberrant expression of MHC class II molecules nor the identity of the TCR can explain these discrepancies.