Characterization of an incompletely assembled major histocompatibility class I molecule (H-2K^b) associated with unusually long peptides: Implications for antigen processing and presentation

We have identified two forms of a major histocompatibility complex (MHC) class I molecule, H-2K^b, distinguishable by specific antibodies through a study of a genetically engineered mouse cell line that overexpresses these molecules. One form, a complex associated with β₂-microglobulin (native, β₂m⁺ class I), is detectable by conformation-dependent antibodies. The other form, which remains after preclearing cell lysates of native class I, is only poorly, if at all, associated with β₂-microglobulin (β₂m^- class I) and is detectable by an antiserum against the cytoplasmic tail region of H-2K molecules. Both forms are also present in normal cell lines. The affinity-purified native class I molecules bind short peptides (8 or 9 residues) and assemble tightly with β₂-microglobulin. In striking contrast, the β₂m^- class I molecules bind peptides that are longer (>15 residues) than those bound to native class I molecules. This finding is consistent with the recent evidence that peptides longer than 8-10 amino acid residues are transported into the endoplasmic reticulum and suggests the possibility of a control step for peptide presentation by MHC in which the incompletely processed peptides bind to the heavy chain and a selected fraction undergoes final processing and presentation on the cell surface.