ALLELE-SPECIFIC DIFFERENCES IN THE INTERACTION OF MHC CLASS-I MOLECULES WITH TRANSPORTERS ASSOCIATED WITH ANTIGEN-PROCESSING

MHC class I molecules bind peptides that are translocated from the cyt osol into the endoplasmic reticulum by the peptide transporter associa ted with antigen processing (TAP), Class I heterodimers have been show n to associate with TAP and are released when loaded with peptide, Her e, we show the existence of two pools of class I heterodimers, one ass ociated with TAP and one that is free, Whereas the free pool is recogn ized by the class I-specific Ab W6/32, the TAP-associated pool is not, Analysis of several class I alleles shows binding to TAP with differe nt efficiencies, even at the earliest time points of MHC class I assem bly, Most HLA-A and -C alleles tested interacted efficiently with TAP, whereas a considerable number of HLA-B alleles associated very ineffi ciently or not at all with TAP. This was also observed in cells with n onfunctional TAP, Sequence comparison of the different class I alleles allowed the definition of amino acids in the peptide binding groove t hat might be involved in TAP association, Binding of peptides to two d ifferent pools of class I heterodimers may ensure efficient peptide as sociation in an environment where peptides have a short life span.