TY - JOUR
T1 - Soluble nonclassical HLA generated by the metalloproteinase pathway
AU - Dong, Yuzhi
AU - Lieskovska, Jaroslava
AU - Kedrin, Dmitriy
AU - Porcelli, Steven
AU - Mandelboim, Ofer
AU - Bushkin, Yuri
N1 - Funding Information:
This work was supported by NIH grants AI 45761 and HL 59835 (Y. B.), AI 45889 (S. P.), and grant 153/00 from the Israeli Science Foundation (O. M.).
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
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 - CD1d
KW - Metalloproteinase
KW - Soluble nonclassical HLA
KW - β-microglobulin
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U2 - 10.1016/S0198-8859(03)00093-4
DO - 10.1016/S0198-8859(03)00093-4
M3 - Article
C2 - 12878359
AN - SCOPUS:0042209905
SN - 0198-8859
VL - 64
SP - 802
EP - 810
JO - Human Immunology
JF - Human Immunology
IS - 8
ER -