CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1

doi:10.1073/pnas.0405266101

CD26 up-regulates expression of CD86 on antigen-presenting cells by means of caveolin-1

^*Department of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan; and ^†Department of Lymphoma/Myeloma, M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030

Communicated by Stuart F. Schlossman, Dana–Farber Cancer Institute, Boston, MA, July 23, 2004 (received for review June 3, 2004)

Abstract

CD26 is a T cell costimulatory molecule with dipeptidyl peptidase IV activity in its extracellular region. We previously reported that recombinant soluble CD26 enhanced T cell proliferation induced by the recall antigen tetanus toxoid (TT). However, the mechanism involved in this enhancement is not yet elucidated. We now demonstrate that CD26 binds Caveolin-1 on antigen-presenting cells, and that residues 201–211 of CD26 along with the serine catalytic site at residue 630 contribute to binding to caveolin-1 scaffolding domain. In addition, after CD26–caveolin-1 interaction on TT-loaded monocytes, caveolin-1 is phosphorylated, which links to activate NF-κB, followed by up-regulation of CD86. Finally, reduced caveolin-1 expression on monocytes inhibits CD26-mediated CD86 up-regulation and abrogates CD26 effect on TT-induced T cell proliferation. Taken together, these results strongly suggest that CD26–caveolin-1 interaction plays a role in the up-regulation of CD86 on TT-loaded monocytes and subsequent engagement with CD28 on T cells, leading to antigen-specific T cell activation.

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: morimoto{at}ims.u-tokyo.ac.jp.
Abbreviations: ADA, adenosine deaminase; APC, antigen-presenting cells; cav-TR, Texas red-conjugated caveolin-1; CBD, caveolin-binding domain; DPPIV, dipeptidyl peptidase IV; EGFP, enhanced GFP; M6P/IGF-IIR, mannose 6-phosphate/insulin-like growth factor II receptor; rsCD26, recombinant soluble CD26; SCD, scaffolding domain; siRNA, small interfering RNA; rsCD26-TR, Texas red-conjugated rsCD26; TT, tetanus toxoid; wt, wild-type; del, deletions.