HLA-B polymorphism affects interaction with multiple endoplasmic reticulum proteins

Héth R. Turnquist, Heather J. Thomas, Kiley R. Prilliman, Charles T. Lutz, William H. Hildebrand, Joyce C Solheim

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

To explore the nature of amino acid substitutions that influence association with TAP, we compared a site-directed mutant of HLA-B*0702 (Y116D) to unmutated HLA-B7 in regard to TAP interaction. We found that the mutant had stronger association with TAP, and, in addition, with tapasin and calreticulin. These data confirm the importance of position 116 for TAP association, and indicate that (1) an aspartic acid at the 116 position can facilitate the interaction, and (2) association with tapasin and calreticulin is affected along with TAP. Furthermore, we tested three natural subtypes of HLA-B15, and found that a B15 subtype with a tyrosine at position 116 (B*1510) was strongly associated not only with TAP, but also with tapasin and calreticulin. In contrast, two B15 subtypes with a serine at position 116 (B*1518 and B*1501) exhibited very little or no association with any of these proteins. Thus, very closely related HLA-B subtypes can differ in regard to interaction with the entire assembly complex. Interestingly, when their surface expression was tested by flow cytometry, the HLA-B15 subtypes with little to no detectable intracellular assembly complex association had a slightly, yet consistently, higher level of the open heavy chain form than did the B15 subtype with intracellular assembly complex association. These data suggest that the relatively low strength or short length of interaction between endoplasmic reticulum proteins and natural HLA class I molecules can decrease their surface stability.

Original languageEnglish (US)
Pages (from-to)3021-3028
Number of pages8
JournalEuropean Journal of Immunology
Volume30
Issue number10
DOIs
StatePublished - Nov 1 2000

Fingerprint

Calreticulin
HLA-B Antigens
HLA-B15 Antigen
Endoplasmic Reticulum
HLA-B7 Antigen
Proteins
Amino Acid Substitution
Aspartic Acid
Serine
Tyrosine
Flow Cytometry
tapasin

Keywords

  • Antigen presentation
  • Calreticulin
  • Chaperone
  • Major histocompatibility complex class I
  • Tapasin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

HLA-B polymorphism affects interaction with multiple endoplasmic reticulum proteins. / Turnquist, Héth R.; Thomas, Heather J.; Prilliman, Kiley R.; Lutz, Charles T.; Hildebrand, William H.; Solheim, Joyce C.

In: European Journal of Immunology, Vol. 30, No. 10, 01.11.2000, p. 3021-3028.

Research output: Contribution to journalArticle

Turnquist, Héth R. ; Thomas, Heather J. ; Prilliman, Kiley R. ; Lutz, Charles T. ; Hildebrand, William H. ; Solheim, Joyce C. / HLA-B polymorphism affects interaction with multiple endoplasmic reticulum proteins. In: European Journal of Immunology. 2000 ; Vol. 30, No. 10. pp. 3021-3028.
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AU - Solheim, Joyce C

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AB - To explore the nature of amino acid substitutions that influence association with TAP, we compared a site-directed mutant of HLA-B*0702 (Y116D) to unmutated HLA-B7 in regard to TAP interaction. We found that the mutant had stronger association with TAP, and, in addition, with tapasin and calreticulin. These data confirm the importance of position 116 for TAP association, and indicate that (1) an aspartic acid at the 116 position can facilitate the interaction, and (2) association with tapasin and calreticulin is affected along with TAP. Furthermore, we tested three natural subtypes of HLA-B15, and found that a B15 subtype with a tyrosine at position 116 (B*1510) was strongly associated not only with TAP, but also with tapasin and calreticulin. In contrast, two B15 subtypes with a serine at position 116 (B*1518 and B*1501) exhibited very little or no association with any of these proteins. Thus, very closely related HLA-B subtypes can differ in regard to interaction with the entire assembly complex. Interestingly, when their surface expression was tested by flow cytometry, the HLA-B15 subtypes with little to no detectable intracellular assembly complex association had a slightly, yet consistently, higher level of the open heavy chain form than did the B15 subtype with intracellular assembly complex association. These data suggest that the relatively low strength or short length of interaction between endoplasmic reticulum proteins and natural HLA class I molecules can decrease their surface stability.

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