Crystal structure of the MHC class I homolog MIC-A, a gamma delta T cell ligand

The major histocompatibility complex (MHC) class I homolog MIC-A functions as a stress-inducible antigen that is recognized by a subset of gamma delta T cells independent of beta(2)-microglobulin and bound peptides. Its cryst al structure reveals a dramatically altered MHC class I fold, both in detai l and overall domain organization. The only remnant of a peptide-binding gr oove is a small cavity formed as the result of disordering a large section of one of the groove-defining helices. Loss of beta(2)-microglobulin bindin g is due to a restructuring of the interaction interfaces. Structural mappi ng of sequence variation suggests potential receptor binding sites on the u nderside of the platform on the side opposite of the surface recognized by alpha beta T cell receptors on MHC class I-peptide complexes.