Characterization of a murine cytomegalovirus class I major histocompatibility complex (MHC) homolog: comparison to MHC molecules and to the human cytomegalovirus MHC homolog.
Both human and murine cytomegaloviruses (HCMV and MCMV) down-regulate expression of conventional class I major histocompatibility complex (MHC) molecules at the surfaces of infected cells. This allows the infected cells to evade recognition by cytotoxic T cells but leaves them susceptible to natural killer cells, which lyse cells that lack class I molecules. Both HCMV and MCMV encode class I MHC heavy-chain homologs that may function in immune response evasion. We previously showed that a soluble form of the HCMV class I homolog (U(L)18) expressed in Chinese hamster ovary cells binds the class I MHC light-chain beta2-microglobulin and a mixture of endogenous peptides (M. L. Fahnestock, J. L. Johnson, R. M. R. Feldman, J. M. Neveu, W. S. Lane, and P. J. Bjorkman, Immunity 3:583-590, 1995). Consistent with this observation, sequence comparisons suggest that U(L)18 contains the well-characterized groove that serves as the binding site in MHC molecules for peptides derived from endogenous and foreign proteins. By contrast, the MCMV homolog (m144) contains a substantial deletion within the counterpart of its alpha2 domain and might not be expected to contain a groove capable of binding peptides. We have now expressed a soluble version of m144 and verified that it forms a heavy chain-beta2-microglobulin complex. By contrast to U(L)18 and classical class I MHC molecules, m144 does not associate with endogenous peptides yet is thermally stable. These results suggest that U(L)18 and m144 differ structurally and might therefore serve different functions for their respective viruses.
Chapman
T L
TL
Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Bjorkman
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018146:Muromegalovirus / Q000235:genetics* / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; D001613:beta 2-Microglobulin; C105297:m144 protein, Mouse cytomegalovirus 1