Differential expression of CLIP:MHC class II and conventional endogenous peptide:MHC class II complexes by thymic epithelial cells and peripheral antigen-presenting cells.
Major histocompatibility complex (MHC) class II molecules expressed by thymic epithelial cells are involved in positive selection of CD4 T cells, whereas the high-avidity interaction of T cell receptors with the endogenous peptide: MHC class II complexes expressed on bone marrow (BM)-derived antigen-presenting cells (APC) and, to a lesser extent, on thymic epithelial cells mediate negative selection. To understand better the generation of the CD4 T cell repertoire both in the thymus and in the periphery we analyzed relative levels of expression of specific endogenous peptide: MHC class II complexes in thymic epithelial cells (TEC) and peripheral APC. Expression of E alpha52-68: I-A(b) and class II-associated invariant chain peptide (CLIP): I-A(b) complexes in thymic epithelial cells and in the bone-marrow derived splenic APC, i.e. B cells, was studied using YAe and 30-2 monoclonal antibodies which are specific for the corresponding complexes. To distinguish between expression of both complexes in radioresistant thymic epithelial elements and radiation sensitive BM-derived APC, radiation BM chimeras were constructed. Using immunohistochemical and immunochemical approaches we demonstrated that the level of expression of E alpha52-68: I-A(b) complexes in thymic epithelial cells is approximately 5-10% of that seen in splenic cells whereas total class II levels were comparable. In contrast, CLIP: I-A(b) complexes are expressed at substantially higher levels in TEC vs. splenic APC. This result demonstrates quantitative differences in expression of distinct peptide: MHC class II complexes in thymic epithelial cells and peripheral splenic APC.
Farr
A
A
Department of Immunology, University of Washington School of Medicine, Seattle 98195, USA.
DeRoos
P C
PC
Eastman
S
S
Rudensky
A Y
AY
D000818:Animals; D000936:Antigen-Antibody Complex / Q000096:biosynthesis*; D000938:Antigen-Presenting Cells / Q000378:metabolism*; D015703:Antigens, CD / Q000096:biosynthesis; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010452:Peptide Biosynthesis; D013950:Thymus Gland / Q000378:metabolism*
D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C045084:invariant chain