Syk tyrosine kinase and B cell antigen receptor (BCR) immunoglobulin-alpha subunit determine BCR-mediated major histocompatibility complex class II-restricted antigen presentation.
Stimulation of CD4(+) helper T lymphocytes by antigen-presenting cells requires the degradation of exogenous antigens into antigenic peptides which associate with major histocompatibility complex (MHC) class II molecules in endosomal or lysosomal compartments. B lymphocytes mediate efficient antigen presentation first by capturing soluble antigens through clonally distributed antigen receptors (BCRs), composed of membrane immunoglobulin (Ig) associated with Ig-alpha/Ig-beta heterodimers which, second, target antigens to MHC class II-containing compartments. We report that antigen internalization and antigen targeting through the BCR or its Ig-alpha-associated subunit to newly synthesized class II lead to the presentation of a large spectrum of T cell epitopes, including some cryptic T cell epitopes. To further characterize the intracellular mechanisms of BCR-mediated antigen presentation, we used two complementary experimental approaches: mutational analysis of the Ig-alpha cytoplasmic tail, and overexpression in B cells of dominant negative syk mutants. Thus, we found that the syk tyrosine kinase, an effector of the BCR signal transduction pathway, is involved in the presentation of peptide- MHC class II complexes through antigen targeting by BCR subunits.
Lankar
D
D
INSERM CJF 95-01, Institut Curie, Section Recherche, Paris, France.
Briken
V
V
Adler
K
K
Weiser
P
P
Cassard
S
S
Blank
U
U
Viguier
M
M
Bonnerot
C
C
D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD / Q000737:chemistry / Q000502:physiology*; D000956:Antigens, Viral / Q000378:metabolism; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D010582:Bacteriophage lambda / Q000276:immunology; D051925:CD79 Antigens; D003593:Cytoplasm / Q000276:immunology; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors / Q000378:metabolism / Q000502:physiology*; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000502:physiology*; D012097:Repressor Proteins / Q000276:immunology; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000502:physiology; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D015703:Antigens, CD; D000956:Antigens, Viral; D051925:CD79 Antigens; C497882:Cd79a protein, mouse; D004268:DNA-Binding Proteins; D004792:Enzyme Precursors; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D012097:Repressor Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C016649:phage repressor proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C000606898:Syk protein, rat