Increased efficiency of folding and peptide loading of mutant MHC class I molecules

Tim Beißbarth, Jiaren Sun, Paula B. Kavathas, Bodo Ortmann

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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, β2 microglobulin and peptide in association with accessory proteins of the peptide loading complex. We show here, that mutations in the α2 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.

Original languageEnglish (US)
Pages (from-to)1203-1213
Number of pages11
JournalEuropean Journal of Immunology
Volume30
Issue number4
StatePublished - 2000

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HLA-A2 Antigen
Major Histocompatibility Complex
Peptides
Endoplasmic Reticulum
Alleles
Calreticulin
Mutation
Mutant Proteins
Binding Sites
Proteins

Keywords

  • Antigen presentation
  • MHC class I
  • Peptide loading complex
  • TAP
  • Tapasin

ASJC Scopus subject areas

  • Immunology

Cite this

Increased efficiency of folding and peptide loading of mutant MHC class I molecules. / Beißbarth, Tim; Sun, Jiaren; Kavathas, Paula B.; Ortmann, Bodo.

In: European Journal of Immunology, Vol. 30, No. 4, 2000, p. 1203-1213.

Research output: Contribution to journalArticle

Beißbarth, T, Sun, J, Kavathas, PB & Ortmann, B 2000, 'Increased efficiency of folding and peptide loading of mutant MHC class I molecules', European Journal of Immunology, vol. 30, no. 4, pp. 1203-1213.
Beißbarth, Tim ; Sun, Jiaren ; Kavathas, Paula B. ; Ortmann, Bodo. / Increased efficiency of folding and peptide loading of mutant MHC class I molecules. In: European Journal of Immunology. 2000 ; Vol. 30, No. 4. pp. 1203-1213.
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