CD99 (MIC2) regulates the LFA-1/1CAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion

Jang Hee Hahn, Min Kyung Kim, Eun Young Choi, Soon Ha Kim, Hae Won Sohn, Don I.I. Ham, Doo Hyun Chung, Tae Jin Kim, Wang Jae Lee, Cheol Keun Park, Howe J. Ree, Seong Hoe Park

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

Despite the fact that integrin-medialed lymphocyte adhesion is a crucial event for an appropriate immune response, little is known about the mechanisms that control the adhesion and deadhesion processes generated by the engagement of CD99 between various types of immune cells. Here we report that the CD99 gene encodes two distinct proteins with opposite functions in the LFA-1/intercellular adhesion molecule 1 (ICAM-1)-mediated cell adhesion process. The two forms of the CD99 protein are produced by alternative splicing of the CD99 gene transcript. The major form induced homotypic adhesion of the human B lymphoblastoid cell line IM-9, whereas the minor, truncated form inhibited the adhesion process. Activation of the major form of CD99 with anti-CD99 monoclonal antibodies induced rapid aggregation of IM-9 cells, which was blocked by the addition of mAbs to LFA-1 or intracellular adhesion molecule 1. Overexpression of the minor truncated form of CD99 markedly down-regulated the expression of LFA-1. The two forms of CD99 are differentially expressed in most human cells tested and are highly conserved in monkey. Taken together, these observations suggest that the two forms of CD99 function in vivo in both positive and negative regulation of LFA-1 -mediated adhesion of lymphocytes during an immune response.

Original languageEnglish
Pages (from-to)2250-2258
Number of pages9
JournalJournal of Immunology
Volume159
Issue number5
StatePublished - 1997
Externally publishedYes

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