Functional expression and recognition of nonclassical MHC class I T10^b is not peptide-dependent

Studies of classical and nonclassical MHC class I molecules have shown that unique peptides are associated and functionally recognized by alloreactive T cells. We have recently shown that an alloreactive TCR-γδ cell recognizes a nonclassical MHC molecule, T10^b. However, T cell recognition of this glycoprotein did not appear to require typical peptide recognition based on studies using transporter-defective mutant cell lines. In the current study, we have analyzed in detail, the role of peptide in T10^b expression and recognition. The findings reveal that the recognition of the nonclassical MHC molecule by TCR-γδ cells is independent of species, tissue type, both the class I and class II Ag processing and presentation pathways, or the presence of peptides. In fact, biochemical analysis of the T10^b chimeric molecule, T10^b/L(d), transfected into CHO cells using radiolabeled [³H]leucine, HPLC, and mass spectrometry suggest that peptides are not associated with this nonclassical class I molecule. Therefore, some class I molecules, e.g., T10^b, do not associate with polymorphic peptides typical of classical MHC class I molecules and can be expressed in the absence of peptides on the cell surface in a functionally active form.