The transmembrane sequence of human histocompatibility leukocyte antigen (HLA)-C as a determinant in inhibition of a subset of natural killer cells

Daniel M. Davis, Ofer Mandelboim, Isabel Luque, Eishi Baba, Jonathan Boyson, Jack L. Strominger

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Molecular interactions with the extracellular domains of class I major histocompatibility complex proteins are major determinants of immune recognition that have been extensively studied both physically and biochemically. However, no immunological function has yet been placed on the transmembrane or cytoplasmic amino acid sequences of these proteins despite strict conservation of unique features within each class I major histocompatibility complex locus. Here we report that lysis by a subset of natural killer (NK) cells inhibited by target cell expression of human histocompatibility leukocyte antigen (HLA)-Cw6 or -Cw7 was not inhibited by expression of chimeric proteins consisting of the extracellular domains of HLA-C and the COOH-terminal portion of HLA-G. Assays using transfectants expressing a variety of HLA-Cw6 mutants identified the transmembrane sequence and, in particular, cysteine at position 309 as necessary for inhibition of 68% (25/37) of NK cell lines and 23% (33/145) of NK clones tested. Moreover, these NK clones inhibited by target cell expression of HLA-Cw6 and dependent upon the transmembrane sequence were found not to express or to only dimly express NK inhibitory receptors (NKIR1) that are EB6/HP3E4-positive. Furthermore, assays using monoclonal antibody blocking suggest that an NK receptor other than NKIR1 or CD94 is responsible for recognition dependent upon the transmembrane sequence of HLA-Cw6.

Original languageEnglish
Pages (from-to)1265-1274
Number of pages10
JournalJournal of Experimental Medicine
Volume189
Issue number8
DOIs
Publication statusPublished - Apr 19 1999
Externally publishedYes

Fingerprint

Histocompatibility Antigens
HLA Antigens
Natural Killer Cells
Major Histocompatibility Complex
Clone Cells
KIR Receptors
Proteins
Cysteine
Amino Acid Sequence
Monoclonal Antibodies
Cell Line

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

The transmembrane sequence of human histocompatibility leukocyte antigen (HLA)-C as a determinant in inhibition of a subset of natural killer cells. / Davis, Daniel M.; Mandelboim, Ofer; Luque, Isabel; Baba, Eishi; Boyson, Jonathan; Strominger, Jack L.

In: Journal of Experimental Medicine, Vol. 189, No. 8, 19.04.1999, p. 1265-1274.

Research output: Contribution to journalArticle

Davis, Daniel M. ; Mandelboim, Ofer ; Luque, Isabel ; Baba, Eishi ; Boyson, Jonathan ; Strominger, Jack L. / The transmembrane sequence of human histocompatibility leukocyte antigen (HLA)-C as a determinant in inhibition of a subset of natural killer cells. In: Journal of Experimental Medicine. 1999 ; Vol. 189, No. 8. pp. 1265-1274.
@article{404caf1a5604479a9a1d0d72269bca39,
title = "The transmembrane sequence of human histocompatibility leukocyte antigen (HLA)-C as a determinant in inhibition of a subset of natural killer cells",
abstract = "Molecular interactions with the extracellular domains of class I major histocompatibility complex proteins are major determinants of immune recognition that have been extensively studied both physically and biochemically. However, no immunological function has yet been placed on the transmembrane or cytoplasmic amino acid sequences of these proteins despite strict conservation of unique features within each class I major histocompatibility complex locus. Here we report that lysis by a subset of natural killer (NK) cells inhibited by target cell expression of human histocompatibility leukocyte antigen (HLA)-Cw6 or -Cw7 was not inhibited by expression of chimeric proteins consisting of the extracellular domains of HLA-C and the COOH-terminal portion of HLA-G. Assays using transfectants expressing a variety of HLA-Cw6 mutants identified the transmembrane sequence and, in particular, cysteine at position 309 as necessary for inhibition of 68{\%} (25/37) of NK cell lines and 23{\%} (33/145) of NK clones tested. Moreover, these NK clones inhibited by target cell expression of HLA-Cw6 and dependent upon the transmembrane sequence were found not to express or to only dimly express NK inhibitory receptors (NKIR1) that are EB6/HP3E4-positive. Furthermore, assays using monoclonal antibody blocking suggest that an NK receptor other than NKIR1 or CD94 is responsible for recognition dependent upon the transmembrane sequence of HLA-Cw6.",
author = "Davis, {Daniel M.} and Ofer Mandelboim and Isabel Luque and Eishi Baba and Jonathan Boyson and Strominger, {Jack L.}",
year = "1999",
month = "4",
day = "19",
doi = "10.1084/jem.189.8.1265",
language = "English",
volume = "189",
pages = "1265--1274",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "8",

}

TY - JOUR

T1 - The transmembrane sequence of human histocompatibility leukocyte antigen (HLA)-C as a determinant in inhibition of a subset of natural killer cells

AU - Davis, Daniel M.

AU - Mandelboim, Ofer

AU - Luque, Isabel

AU - Baba, Eishi

AU - Boyson, Jonathan

AU - Strominger, Jack L.

PY - 1999/4/19

Y1 - 1999/4/19

N2 - Molecular interactions with the extracellular domains of class I major histocompatibility complex proteins are major determinants of immune recognition that have been extensively studied both physically and biochemically. However, no immunological function has yet been placed on the transmembrane or cytoplasmic amino acid sequences of these proteins despite strict conservation of unique features within each class I major histocompatibility complex locus. Here we report that lysis by a subset of natural killer (NK) cells inhibited by target cell expression of human histocompatibility leukocyte antigen (HLA)-Cw6 or -Cw7 was not inhibited by expression of chimeric proteins consisting of the extracellular domains of HLA-C and the COOH-terminal portion of HLA-G. Assays using transfectants expressing a variety of HLA-Cw6 mutants identified the transmembrane sequence and, in particular, cysteine at position 309 as necessary for inhibition of 68% (25/37) of NK cell lines and 23% (33/145) of NK clones tested. Moreover, these NK clones inhibited by target cell expression of HLA-Cw6 and dependent upon the transmembrane sequence were found not to express or to only dimly express NK inhibitory receptors (NKIR1) that are EB6/HP3E4-positive. Furthermore, assays using monoclonal antibody blocking suggest that an NK receptor other than NKIR1 or CD94 is responsible for recognition dependent upon the transmembrane sequence of HLA-Cw6.

AB - Molecular interactions with the extracellular domains of class I major histocompatibility complex proteins are major determinants of immune recognition that have been extensively studied both physically and biochemically. However, no immunological function has yet been placed on the transmembrane or cytoplasmic amino acid sequences of these proteins despite strict conservation of unique features within each class I major histocompatibility complex locus. Here we report that lysis by a subset of natural killer (NK) cells inhibited by target cell expression of human histocompatibility leukocyte antigen (HLA)-Cw6 or -Cw7 was not inhibited by expression of chimeric proteins consisting of the extracellular domains of HLA-C and the COOH-terminal portion of HLA-G. Assays using transfectants expressing a variety of HLA-Cw6 mutants identified the transmembrane sequence and, in particular, cysteine at position 309 as necessary for inhibition of 68% (25/37) of NK cell lines and 23% (33/145) of NK clones tested. Moreover, these NK clones inhibited by target cell expression of HLA-Cw6 and dependent upon the transmembrane sequence were found not to express or to only dimly express NK inhibitory receptors (NKIR1) that are EB6/HP3E4-positive. Furthermore, assays using monoclonal antibody blocking suggest that an NK receptor other than NKIR1 or CD94 is responsible for recognition dependent upon the transmembrane sequence of HLA-Cw6.

UR - http://www.scopus.com/inward/record.url?scp=0033583430&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033583430&partnerID=8YFLogxK

U2 - 10.1084/jem.189.8.1265

DO - 10.1084/jem.189.8.1265

M3 - Article

VL - 189

SP - 1265

EP - 1274

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 8

ER -