HLA-F is a predominantly empty, intracellular, TAP-associated MHC class Ibprotein with a restricted expression pattern

HLA-F is currently the most enigmatic of the human MHC-encoded class Ib gen es. We have investigated the expression of HLA-F using a specific Ab raised against a synthetic peptide corresponding to amino acids 61-84 in the alph a 1 domain of the predicted HLA-F protein. HLA-F is expressed as a beta(2)- microglobulin-associated, 42-kDa protein that shows a restricted tissue dis tribution, To date, we have detected this product only in peripheral blood B cells, B cell lines, and tissues containing B cells, in particular adult tonsil and fetal liver, a major site of B cell development. Thermostability assays suggest that HLA-F is expressed as an empty heterodimer devoid of p eptide. Consistent with this, studies using endoglycosidase-a and cell surf ace immunoprecipitations also indicate that the overwhelming majority of HL A-F contains an immature oligosaccharide component and is expressed inside the cell. We have found that IFN-gamma treatment induces expression of HLA- F mRNA and HLA-F protein, but that this does not result in concomitant cell surface expression. HLA-F associates with at least two components of the c onventional class I assembly pathway, calreticulin and TAP. The unusual cha racteristics of the predicted peptide-binding groove together with the pred ominantly intracellular localization raise the possibility that HLA-F may b e capable of binding only a restricted set of peptides.