Soluble nonclassical HLA generated by the metalloproteinase pathway

Yuzhi Dong, Jaroslava Lieskovska, Dmitriy Kedrin, Steven A. Porcelli, Ofer Mandelboim, Yuri Bushkin

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Soluble human leukocyte antigens (HLA-A, -B, and -C) proteins can be generated by a membrane-bound metalloproteinase (MPase). The MPase-mediated pathway produces soluble nonconformed HLA proteins susceptible to further degradation, and also HLA proteins with high affinity peptides stable at physiologic temperatures. Accessibility of classical HLA to the MPase cleavage inversely correlates with stability of heavy chain (HC) interactions with β2-microglobulin (β2M). Whether a MPase is involved in release of soluble non-classical HLA or CD1 proteins is unknown. We have investigated this question with transfectants expressing full-length HLA proteins. Native surface HLA-E and -G complexes, similar to HLA-A2, were unstable at low pH and dissociated giving rise to β2m-free HC. Furthermore, HLA-E and -G proteins, similar to HLA-A2, were readily released from cell surface into supernatants as soluble 37-kilodalton β2m-free HC. However, the stability of surface CD1d complexes was not affected by pH changes and no soluble CD1d was detected. Because β2m-free CD1d HC were expressed on cells, the lack of cleaved soluble products cannot be explained by high stability of native complexes. Instead, absence of a CD1d-specific MPase in these cells or its impaired interactions with substrate HC may be responsible.

Original languageEnglish (US)
Pages (from-to)802-810
Number of pages9
JournalHuman Immunology
Volume64
Issue number8
DOIs
StatePublished - Aug 1 2003

Fingerprint

Metalloproteases
HLA-G Antigens
HLA-A2 Antigen
Proteins
HLA-A Antigens
HLA-B Antigens
HLA Antigens
Protein C
GTP-Binding Proteins
Peptides
Temperature
Membranes

Keywords

  • β-microglobulin
  • CD1d
  • Metalloproteinase
  • Soluble nonclassical HLA

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Soluble nonclassical HLA generated by the metalloproteinase pathway. / Dong, Yuzhi; Lieskovska, Jaroslava; Kedrin, Dmitriy; Porcelli, Steven A.; Mandelboim, Ofer; Bushkin, Yuri.

In: Human Immunology, Vol. 64, No. 8, 01.08.2003, p. 802-810.

Research output: Contribution to journalArticle

Dong, Y, Lieskovska, J, Kedrin, D, Porcelli, SA, Mandelboim, O & Bushkin, Y 2003, 'Soluble nonclassical HLA generated by the metalloproteinase pathway', Human Immunology, vol. 64, no. 8, pp. 802-810. https://doi.org/10.1016/S0198-8859(03)00093-4
Dong, Yuzhi ; Lieskovska, Jaroslava ; Kedrin, Dmitriy ; Porcelli, Steven A. ; Mandelboim, Ofer ; Bushkin, Yuri. / Soluble nonclassical HLA generated by the metalloproteinase pathway. In: Human Immunology. 2003 ; Vol. 64, No. 8. pp. 802-810.
@article{6cfcb5bccfe84fa7bdcdd37d592864b7,
title = "Soluble nonclassical HLA generated by the metalloproteinase pathway",
abstract = "Soluble human leukocyte antigens (HLA-A, -B, and -C) proteins can be generated by a membrane-bound metalloproteinase (MPase). The MPase-mediated pathway produces soluble nonconformed HLA proteins susceptible to further degradation, and also HLA proteins with high affinity peptides stable at physiologic temperatures. Accessibility of classical HLA to the MPase cleavage inversely correlates with stability of heavy chain (HC) interactions with β2-microglobulin (β2M). Whether a MPase is involved in release of soluble non-classical HLA or CD1 proteins is unknown. We have investigated this question with transfectants expressing full-length HLA proteins. Native surface HLA-E and -G complexes, similar to HLA-A2, were unstable at low pH and dissociated giving rise to β2m-free HC. Furthermore, HLA-E and -G proteins, similar to HLA-A2, were readily released from cell surface into supernatants as soluble 37-kilodalton β2m-free HC. However, the stability of surface CD1d complexes was not affected by pH changes and no soluble CD1d was detected. Because β2m-free CD1d HC were expressed on cells, the lack of cleaved soluble products cannot be explained by high stability of native complexes. Instead, absence of a CD1d-specific MPase in these cells or its impaired interactions with substrate HC may be responsible.",
keywords = "β-microglobulin, CD1d, Metalloproteinase, Soluble nonclassical HLA",
author = "Yuzhi Dong and Jaroslava Lieskovska and Dmitriy Kedrin and Porcelli, {Steven A.} and Ofer Mandelboim and Yuri Bushkin",
year = "2003",
month = "8",
day = "1",
doi = "10.1016/S0198-8859(03)00093-4",
language = "English (US)",
volume = "64",
pages = "802--810",
journal = "Human Immunology",
issn = "0198-8859",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - Soluble nonclassical HLA generated by the metalloproteinase pathway

AU - Dong, Yuzhi

AU - Lieskovska, Jaroslava

AU - Kedrin, Dmitriy

AU - Porcelli, Steven A.

AU - Mandelboim, Ofer

AU - Bushkin, Yuri

PY - 2003/8/1

Y1 - 2003/8/1

N2 - Soluble human leukocyte antigens (HLA-A, -B, and -C) proteins can be generated by a membrane-bound metalloproteinase (MPase). The MPase-mediated pathway produces soluble nonconformed HLA proteins susceptible to further degradation, and also HLA proteins with high affinity peptides stable at physiologic temperatures. Accessibility of classical HLA to the MPase cleavage inversely correlates with stability of heavy chain (HC) interactions with β2-microglobulin (β2M). Whether a MPase is involved in release of soluble non-classical HLA or CD1 proteins is unknown. We have investigated this question with transfectants expressing full-length HLA proteins. Native surface HLA-E and -G complexes, similar to HLA-A2, were unstable at low pH and dissociated giving rise to β2m-free HC. Furthermore, HLA-E and -G proteins, similar to HLA-A2, were readily released from cell surface into supernatants as soluble 37-kilodalton β2m-free HC. However, the stability of surface CD1d complexes was not affected by pH changes and no soluble CD1d was detected. Because β2m-free CD1d HC were expressed on cells, the lack of cleaved soluble products cannot be explained by high stability of native complexes. Instead, absence of a CD1d-specific MPase in these cells or its impaired interactions with substrate HC may be responsible.

AB - Soluble human leukocyte antigens (HLA-A, -B, and -C) proteins can be generated by a membrane-bound metalloproteinase (MPase). The MPase-mediated pathway produces soluble nonconformed HLA proteins susceptible to further degradation, and also HLA proteins with high affinity peptides stable at physiologic temperatures. Accessibility of classical HLA to the MPase cleavage inversely correlates with stability of heavy chain (HC) interactions with β2-microglobulin (β2M). Whether a MPase is involved in release of soluble non-classical HLA or CD1 proteins is unknown. We have investigated this question with transfectants expressing full-length HLA proteins. Native surface HLA-E and -G complexes, similar to HLA-A2, were unstable at low pH and dissociated giving rise to β2m-free HC. Furthermore, HLA-E and -G proteins, similar to HLA-A2, were readily released from cell surface into supernatants as soluble 37-kilodalton β2m-free HC. However, the stability of surface CD1d complexes was not affected by pH changes and no soluble CD1d was detected. Because β2m-free CD1d HC were expressed on cells, the lack of cleaved soluble products cannot be explained by high stability of native complexes. Instead, absence of a CD1d-specific MPase in these cells or its impaired interactions with substrate HC may be responsible.

KW - β-microglobulin

KW - CD1d

KW - Metalloproteinase

KW - Soluble nonclassical HLA

UR - http://www.scopus.com/inward/record.url?scp=0042209905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0042209905&partnerID=8YFLogxK

U2 - 10.1016/S0198-8859(03)00093-4

DO - 10.1016/S0198-8859(03)00093-4

M3 - Article

VL - 64

SP - 802

EP - 810

JO - Human Immunology

JF - Human Immunology

SN - 0198-8859

IS - 8

ER -