An extensive region of an MHC class I α2 domain loop influences interaction with the assembly complex

Yik Y L Yu, Heth R. Turnquist, Nancy B. Myers, Ganesaratnam K. Balendiran, Ted H. Hansen, Joyce C Solheim

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

Presentation of antigenic peptides to CTLs at the cell surface first requires assembly of MHC class I with peptide and β2-microglobulin in the endoplasmic reticulum. This process involves an assembly complex of several proteins, including TAP, tapasin, and calreticulin, all of which associate specifically with the β2-microglobulin-assembled, open form of the class I heavy chain. To better comprehend at a molecular level the regulation of class I assembly, we have assessed the influence of multiple individual amino acid substitutions in the MHC class I α2 domain on interaction with TAP, tapasin, and calreticulin. In this report, we present evidence indicating that many residues surrounding position 134 in H-2L(d) influence interaction with assembly complex components. Most mutations decreased association, but one (L(d)K131D) strongly increased it. The L(d) mutants, with the exception of L(d)K131D, exhibited characteristics suggesting suboptimal intracellular peptide loading, similar to the phenotype of L(d) expressed in a tapasin- deficient cell line. Notably, K131D was less peptide inducible than wild-type L(d), which is consistent with its unusually strong association with the endoplasmic reticulum assembly complex.

Original languageEnglish (US)
Pages (from-to)4427-4433
Number of pages7
JournalJournal of Immunology
Volume163
Issue number8
StatePublished - Oct 20 1999

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Calreticulin
Peptides
Endoplasmic Reticulum
Amino Acid Substitution
Phenotype
Cell Line
Mutation
tapasin
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Yu, Y. Y. L., Turnquist, H. R., Myers, N. B., Balendiran, G. K., Hansen, T. H., & Solheim, J. C. (1999). An extensive region of an MHC class I α2 domain loop influences interaction with the assembly complex. Journal of Immunology, 163(8), 4427-4433.

An extensive region of an MHC class I α2 domain loop influences interaction with the assembly complex. / Yu, Yik Y L; Turnquist, Heth R.; Myers, Nancy B.; Balendiran, Ganesaratnam K.; Hansen, Ted H.; Solheim, Joyce C.

In: Journal of Immunology, Vol. 163, No. 8, 20.10.1999, p. 4427-4433.

Research output: Contribution to journalArticle

Yu, YYL, Turnquist, HR, Myers, NB, Balendiran, GK, Hansen, TH & Solheim, JC 1999, 'An extensive region of an MHC class I α2 domain loop influences interaction with the assembly complex', Journal of Immunology, vol. 163, no. 8, pp. 4427-4433.
Yu YYL, Turnquist HR, Myers NB, Balendiran GK, Hansen TH, Solheim JC. An extensive region of an MHC class I α2 domain loop influences interaction with the assembly complex. Journal of Immunology. 1999 Oct 20;163(8):4427-4433.
Yu, Yik Y L ; Turnquist, Heth R. ; Myers, Nancy B. ; Balendiran, Ganesaratnam K. ; Hansen, Ted H. ; Solheim, Joyce C. / An extensive region of an MHC class I α2 domain loop influences interaction with the assembly complex. In: Journal of Immunology. 1999 ; Vol. 163, No. 8. pp. 4427-4433.
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