Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement.

Abstract:

:T lymphocyte receptor CTLA-4 binds costimulatory molecules CD80 (B7-1) and CD86 (B7-2) with high avidity and negatively regulates T cell activation. CTLA-4 functions at the cell surface, yet is primarily localized in intracellular vesicles. Here, we demonstrate cycling of CTLA-4 between intracellular stores and the cell surface. Intracellular vesicles containing CTLA-4 overlapped with endocytic compartment(s) and with perforin-containing secretory granules. Cell surface expression of CTLA-4 was rapidly increased by raising intracellular calcium levels. During T cell activation, intracellular and cell surface CTLA-4 became focused towards sites of TCR activation. Cycling and directional control of CTLA-4 expression may regulate its functional interaction with APCs bearing peptide-MHC complexes of appropriate specificity and avidity.

journal_name

Immunity

journal_title

Immunity

authors

Linsley PS,Bradshaw J,Greene J,Peach R,Bennett KL,Mittler RS

doi

10.1016/s1074-7613(00)80480-x

subject

Has Abstract

pub_date

1996-06-01 00:00:00

pages

535-43

issue

6

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(00)80480-X

journal_volume

4

pub_type

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