Differential expression of leukocyte receptor complex-encoded Ig-like receptors correlates with the transition from effector to memory CTL.
The human leukocyte receptor complex (LRC) on chromosome 19q13.4 encodes Ig superfamily receptors expressed on hemopoietic cells. Killer Ig-like receptors (KIR) are expressed in cytotoxic lymphocytes but other LRC molecules (Ig-like transcript(ILT)/leukocyte Ig-like receptor (LIR)) are more ubiquitous. We investigated expression of the ILT2/LIR1 inhibitory receptor compared with the related KIR. Both ILT2/LIR1 and KIR were expressed by peripheral CD8(+) T cells with a memory/effector phenotype. ILT2/LIR1(+) T cells demonstrated diverse TCRBV repertoires in contrast to KIR(+) T cells, while numbers of peripheral ILT2/LIR1(+) T cells were greater than KIR(+) T cells and the majority of ILT2/LIR1(+) T cells did not coexpress KIR. Analysis of CD8(+) T cells with specific HLA class I tetramers confirmed this pattern of expression, indicating differential regulation of LRC gene expression in T lymphocytes. Only a minor proportion of ILT2/LIR1(+) KIR(-) clones survived in vitro cloning, were more susceptible to anti-CD3 or cognate peptide induced cell death than KIR(+) T cells and exhibited lower levels of the Bcl-2 survival molecule. Our results indicate a sequential program of LRC-encoded receptor expression with initial ILT2/LIR1 expression in effector T cells and KIR gene transcription in the minor proportion of expanded clones which survives activation-induced cell death to become long term memory T cells.
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA. neil.young@nds.ox.ac.uk
N T
NT
Young
M
M
Uhrberg
J H
JH
Phillips
L L
LL
Lanier
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P
Parham
D015703:Antigens, CD; D016923:Cell Death / Q000276:immunology; D002461:Cell Line, Transformed; D002999:Clone Cells; D005434:Flow Cytometry; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005810:Multigene Family / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D054340:Receptors, KIR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D007136:Immunoglobulins; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D054340:Receptors, KIR