HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rosen, D. B. Articles by Lanier, L. L. Search for Related Content PubMed PubMed Citation Articles by Rosen, D. B. Articles by Lanier, L. L.

Functional Consequences of Interactions between Human NKR-P1A and Its Ligand LLT1 Expressed on Activated Dendritic Cells and B Cells¹

David B. Rosen^*, Wei Cao, Danielle T. Avery, Stuart G. Tangye, Yong-Jun Liu, J. P. Houchins and Lewis L. Lanier^2,*

^* Department of Microbiology and Immunology, Biomedical Sciences Graduate Program, and Cancer Research Institute, University of California, San Francisco, CA 94143; Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030; Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia; and R&D Systems, Minneapolis, MN 55413

Lectin-like transcript-1 (LLT1) (also named osteoclast inhibitory lectin or CLEC2D) is a ligand for the human NKR-P1A (CD161) receptor, present on NK cells and T cells. To further understand the physiological relevance of this interaction, we developed mAbs against LLT1, characterized the expression pattern of LLT1, and explored the functional consequence of LLT1 engagement of the NKR-P1A receptor on NK cells and T cells. LLT1 is expressed on TLR-activated plasmacytoid dendritic, TLR-activated monocyte-derived dendritic cells, and on B cells stimulated through TLR9, surface Ig, or CD40. Interactions between NKR-P1A on NK cells and LLT1 on target cells inhibit NK cell-mediated cytotoxicity and cytokine production and can inhibit TNF- production by TCR-activated NKR-P1A⁺ CD8⁺ T cells. In contrast, NKR-P1A failed to inhibit or augment the TCR-dependent activation of NKR-P1A-bearing CD4⁺ T cells. Expression of LLT1 on activated dendritic cells and B cells suggests that it might regulate the cross-talk between NK cells and APCs.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grant AI068129. L.L.L. is an American Cancer Society Research Professor, and D.B.R. was supported by a Genentech Graduate Student Fellowship and a University of California Chancellor’s Research Fellowship. J.P.H. is employed and supported by R&D Systems, Inc.

² Address correspondence and reprint requests to Dr. Lewis L. Lanier, University of California, 513 Parnassus Avenue, Box 0414, HSE 1001G, San Francisco, CA 94143. E-mail address: lewis.lanier{at}ucsf.edu

³ Abbreviations used in this paper: LLT1, lectin-like transcript-1; AICL, activation-induced C-type lectin; MOI, multiplicity of infection; pDC, plasmacytoid dendritic cell; Mo-DC, monocyte-derived dendritic cell; PNGase F, protein N-glycanase F; DC, dendritic cell.