A subset of T cells recognizes antigenic complexes formed by CD1 molecules (CD1a, b, c or d) associated with self or microbial glycolipid antigens, which in some instances become immunogenic only after being processed. CD1e is the fifth member of the human CD1 family and is the only isoform whose function was unknown. In immature dendritic cell (DC) CD1e resides in Golgi compartments and upon DC maturation it reaches acidic late endosomes/lysosomes where it is cleaved and accumulates in a stable soluble form. Remarkably, unlike the other CD1 molecules, CD1e never transits through the cell surface, a characteristic that excludes its direct interaction with T cells. Here, it’s demonstrated that the mycobacterial glicolipid antigen hexamannosylated-phosphatidyl-myo-inositol (PIM6) stimulates CD1b-restricted specific T cells only after digestion of the four terminal mannoses by lysosomal α-mannosidase, and that lysosomal CD1e is required for this processing. These data show that soluble CD1e optimally binds glycolipids at acidic pH and cooperates in the digestion in vitro of PIM6 by α- mannosidase. Furthermore, CD1b and CD1e must colocalize in late endosomes/lysosomes compartments to get presentation of CD1b-restricted CD1e-dependent antigens and the intracellular soluble CD1e is likely to be the active form. On the contrary, presentation of those glycolipids that do not require processing (like self-glycosphingolipids or mycobacterial diacetylsulfoglycolipid) is CD1e independent. These findings support a model in which CD1e serves as a chaperone assisting enzymatic processing of microbial glycolipid antigens thus expanding the repertoire of glycolipidic T cell antigens and optimizing the anti-microbial immune responses.
Mariotti, S. (2008). Role of CD1e in microbial glycolipid antigen processing and presentation to unconventional T lymphocytes.
|Titolo:||Role of CD1e in microbial glycolipid antigen processing and presentation to unconventional T lymphocytes|
|Data di pubblicazione:||1-set-2008|
|Anno Accademico:||A.A. 2005/2006|
|Corso di dottorato:||Microbiologia Medica ed Immunologia|
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Tipologia:||Tesi di dottorato|
|Citazione:||Mariotti, S. (2008). Role of CD1e in microbial glycolipid antigen processing and presentation to unconventional T lymphocytes.|
|Appare nelle tipologie:||07 - Tesi di dottorato|