Dissociation of beta 2-microglobulin leads to the accumulation of a substantial pool of inactive class I MHC heavy chains on the cell surface.
A large pool of free class I heavy chains is detected in situ on the plasma membrane of living cells. These chains are present on cells of different MHC genotypes and appear to exist under physiological conditions in vivo. These molecules arise from the dissociation of previously assembled class I heterodimers at the cell surface. The ratio of intact to dissociated heterodimers is strongly affected by the occupancy of the peptide-binding site of the class I molecule. Upon dissociation of the heterodimer, the class I molecule is functionally inactive. These findings may help to explain why class I molecules on the cell surface are unreceptive to binding peptides yet readily associate with peptides in the presence of exogenous beta 2-microglobulin. These results have implications for understanding the distinct functions of class I versus class II molecules and how the immunological identity of cells is preserved.
Rock
K L
KL
Division of Lymphocyte Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Gamble
S
S
Rothstein
L
L
Gramm
C
C
Benacerraf
B
B
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D046911:Macromolecular Substances; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D001613:beta 2-Microglobulin / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D046911:Macromolecular Substances; D011971:Receptors, Immunologic; C027292:beta 2 microglobulin receptor; D001613:beta 2-Microglobulin