Comodulation of CXCR4 and CD26 in Human Lymphocytes

Carolina Herrera,Chikao Morimoto,Julià Blanco,Josefa Mallol,Fernando Arenzana,Carmen Lluis,Rafael Franco

doi:10.1074/jbc.m004586200

Abstract

We provide convergent and multiple evidence for a CD26/CXCR4 interaction. Thus, CD26 codistributes with CXCR4, and both coimmunoprecipitate from membranes of T (CD4(+)) and B (CD4(-)) cell lines. Upon induction with stromal cell-derived factor 1alpha (SDF-1alpha), CD26 is cointernalized with CXCR4. CXCR4-mediated down-regulation of CD26 is not induced by antagonists or human immunodeficiency virus (HIV)-1 gp120. SDF-1alpha-mediated down-regulation of CD26 is not blocked by pertussis toxin but does not occur in cells expressing mutant CXCR4 receptors unable to internalize. Codistribution and cointernalization also occurs in peripheral blood lymphocytes. Since CD26 is a cell surface endopeptidase that has the capacity to cleave SDF-1alpha, the CXCR4.CD26 complex is likely a functional unit in which CD26 may directly modulate SDF-1alpha-induced chemotaxis and antiviral capacity. CD26 anchors adenosine deaminase (ADA) to the lymphocyte cell surface, and this interaction is blocked by HIV-1 gp120. Here we demonstrate that gp120 interacts with CD26 and that gp120-mediated disruption of ADA/CD26 interaction is a consequence of a first interaction of gp120 with a domain different from the ADA binding site. SDF-1alpha and gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize and in which ADA is not present. The physical association of CXCR4 and CD26, direct or part of a supramolecular structure, suggests a role on the function of the immune system and the pathophysiology of HIV infection.

Highlights

CD26 is a widely distributed lymphocyte activation antigen that displays dipeptidyl peptidase IV activity in its extracellular domain
Given the functional relationship between dipeptidyl peptidase IV activity of CD26 and CXCR4, and the role of CXCR4 in gp120-mediated inhibition of adenosine deaminase (ADA) binding to CD26, we have studied the distribution of these proteins on the surface of human lymphocytes
In this paper we demonstrate for the first time that CD26 and CXCR4 interact in primary lymphocytes from human blood and in T and B cell lines

Summary

Introduction

CD26 is a widely distributed lymphocyte activation antigen that displays dipeptidyl peptidase IV activity in its extracellular domain. CXCR4 Coimmunoprecipitates with CD26 —The high degree of colocalization between CD26 and CXCR4 on the Jurkat J32 and SKW6.4 cell surface, and the coclustering of these proteins in the pseudopodia induced by gp120 in T cells, suggest a molecular interaction between both molecules.

Results

Conclusion