Increased efficiency of folding and peptide loading of mutant MHC class I molecules.
Eur J Immunol
; 30(4): 1203-13, 2000 Apr.
Article
en En
| MEDLINE
| ID: mdl-10760810
Class I molecules, encoded by diverse alleles at several loci of the major histocompatibility complex (MHC) are assembled in the endoplasmic reticulum (ER) from heavy chain, beta2 microglobulin and peptide in association with accessory proteins of the peptide loading complex. We show here, that mutations in the alpha2 domain (Q115A; D122A) of the human class I allele HLA-A2 cause a lack of apparent association with the loading complex and a faster assembly. Despite the drastically reduced association with the TAP loading complex, i. e. less than 20 % of HLA-A2 expressed in the cells can be co-precipitated with either TAP, calreticulin or tapasin, the mutant proteins are expressed on the cell surface in a stable conformation, and bind a complex set of peptides almost identical to that of wild-type HLA-A2. Furthermore, the mutant class I molecules are more rapidly exported from the ER than wild-type HLA-A2 and undergo faster maturation. The mutation Q115A does not destroy a binding site for the loading complex as this HLA-A2 mutant associates with the loading complex when peptide supply is limited. The association of class I molecules with the TAP-associated loading complex appears to be a reflection of how quickly the stable conformation is gained.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Antígeno HLA-A2
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Pliegue de Proteína
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Presentación de Antígeno
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Mutación
Límite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Año:
2000
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Alemania