Structural studies of class I major histocompatibility complex proteins: insights into antigen presentation

1995 ◽  
Vol 9 (1) ◽  
pp. 26-36 ◽  
Author(s):  
Aideen C. M. Young ◽  
Stanley G. Nathenson ◽  
James C. Sacchettini
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Class I ◽  
Structural Studies ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Major Histocompatibility Complex Proteins

scholarly journals A gene required for class II-restricted antigen presentation maps to the major histocompatibility complex.

1991 ◽  
Vol 174 (6) ◽  
pp. 1607-1615 ◽  
Author(s):  
E Mellins ◽  
S Kempin ◽  
L Smith ◽  
T Monji ◽  
D Pious
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Somatic Cell ◽  
Class Ii ◽  
Homozygous Deletion ◽  
Class I ◽  
Somatic Cell Hybrids ◽  
Major Histocompatibility ◽  
Cell Hybrids ◽  
Histocompatibility Complex

We have previously described a set of mutants (16.23-selected mutants) of a B lymphoblastoid cell line that are defective in the presentation of intact proteins to class II-restricted T cells, but effectively present immunogenic peptides. The mutations in these mutants are recessive in somatic cell hybrids and are not in Class II structural genes. Here, we report on a unique mutant, 5.2.4, in which a similar defect in class II-restricted antigen presentation has occurred in association with a one-megabase homozygous deletion in the class II region of the major histocompatibility complex (MHC). The defects in class II presentation among three of the 16.23-selected mutants, and between these mutants and 5.2.4, are noncomplementary in somatic cell hybrids. This suggests that the class II presentation-defective phenotype in all four mutants results from lesions in a single MHC-linked gene, a conclusion strengthened by the finding that in a hybrid made with a second, unrelated MHC deletion mutant, T2, the class II presentation defect in a 16.23-selected mutant is also not complemented. Mutant 5.2.4, in addition to its class II presentation defect, is also defective in surface expression of MHC class I molecules, most likely because its deletion encompasses the peptide supply factor 1 gene, whose function is known to be required for normal abundance of cell surface class I molecules. However, the surface abundance of class I molecules is normal in the 16.23-selected mutants, suggesting that the lesions affecting class I surface abundance and class II presentation result from mutations in different genes.

scholarly journals Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

2015 ◽  
Vol 84 (2) ◽  
pp. 480-490 ◽  
Author(s):  
Erik D. Cram ◽  
Ryan S. Simmons ◽  
Amy L. Palmer ◽  
William H. Hildebrand ◽  
Daniel D. Rockey ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Content Type ◽  
Histocompatibility Complex ◽  
Peptide Presentation ◽  
Mhc Class I Antigen ◽  
Self Antigen

The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8+cytotoxic T lymphocytes.Chlamydiaspp. are obligate intracellular bacteria and, as such, should be targeted by CD8+T cells. It is likely thatChlamydiaspp. have evolved mechanisms to avoid the CD8+killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of variousChlamydiaspecies to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced self-peptide presentation was detected only when presentation was restricted todefectiveribosomalproducts, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest thatChlamydiaspp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins.

scholarly journals Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment.

1992 ◽  
Vol 176 (3) ◽  
pp. 729-738 ◽  
Author(s):  
M del Val ◽  
H Hengel ◽  
H Häcker ◽  
U Hartlaub ◽  
T Ruppert ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Antigen Presentation ◽  
Mhc Class I ◽  
Heavy Chain ◽  
Class I ◽  
Antigenic Peptides ◽  
Major Histocompatibility ◽  
Early Genes ◽  
Histocompatibility Complex ◽  
Golgi Compartment

Selective expression of murine cytomegalovirus (MCMV) immediate-early (IE) genes leads to the presentation by the major histocompatibility complex (MHC) class I molecule Ld of a peptide derived from MCMV IE protein pp89 (Reddehase, M.J., J. B. Rothbard, and U.H. Koszinowski. 1989. Nature (Lond.). 337:651). Characterization of endogenous antigenic peptides identified the pp89 peptide as the nonapeptide 168YPHFMPTNL176 (del Val, M., H.-J. Schlicht, T. Ruppert, M.J. Reddehase, and U.H. Koszinowski. 1991. Cell. 66:1145). Subsequent expression of MCMV early genes prevents presentation of pp89 (del Val, M., K. Münch, M.J. Reddehase, and U.H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism by which MCMV early genes interfere with antigen presentation. Expression of the IE promoter-driven bacterial gene lacZ by recombinant MCMV subjected antigen presentation of beta-galactosidase to the same control and excluded antigen specificity. The Ld-dependent presence of naturally processed antigenic peptides also in nonpresenting cells located the inhibitory function subsequent to the step of antigen processing. The finding that during the E phase of MCMV gene expression the MHC class I heavy chain glycosylation remained in an Endo H-sensitive form suggested a block within the endoplasmic reticulum/cis-Golgi compartment. The failure to present antigenic peptides was explained by a general retention of nascent assembled trimolecular MHC class I complexes. Accordingly, at later stages of infection a significant decrease of surface MHC class I expression was seen, whereas other membrane glycoproteins remained unaffected. Thus, MCMV E genes endow this virus with an effective immune evasion potential. These results also indicate that the formation of the trimolecular complex of MHC class I heavy chain, beta 2-microglobulin, and the finally trimmed peptide is completed before entering the medial-Golgi compartment.

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