Presentation of ovalbumin internalized via the immunoglobulin-A Fc receptor is enhanced through Fc receptor gamma-chain signaling.
The mechanism of enhanced presentation of ovalbumin (OVA) internalized as immunoglobulin A (IgA)-OVA via the IgA Fc receptor (FcalphaR) was analyzed by focusing on the role of the FcalphaR-associated gamma chain. Comparison of B-cell transfectants expressing FcalphaR plus wild-type (WT) gamma chain or gamma chain in which the immunoreceptor tyrosine-based activation motif (ITAM) was altered by tyrosine mutation or substitution with the ITAM of FcgammaRIIA showed that signaling-competent ITAM was not required for endocytosis of IgA-OVA. However, antigen presentation was impaired by ITAM changes. Signaling-competent gamma-chain ITAM appeared necessary for transport of ligated FcalphaR to a lamp-1(+) late endocytic compartment for remodeling and/or activation of that compartment and also for efficient degradation of IgA complexes. Moreover, FcalphaR ligation also activated efficient processing of nonreceptor-targeted antigen. The results suggest that gamma-chain signaling activates the antigen processing compartment.
Shen
L
L
Department of Immunology and Microbiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA. lilian.shen@dartmouth.edu
van Egmond
M
M
Siemasko
K
K
Gao
H
H
Wade
T
T
Lang
M L
ML
Clark
M
M
van De Winkel
J G
JG
Wade
W F
WF
D020816:Amino Acid Motifs / Q000235:genetics / Q000276:immunology / Q000502:physiology; D019943:Amino Acid Substitution; D017951:Antigen Presentation / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D004705:Endocytosis / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism*; D021122:Protein Subunits; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D011961:Receptors, Fc / Q000276:immunology / Q000378:metabolism*; D017452:Receptors, IgG / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology*; D014162:Transfection; D014443:Tyrosine
D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D021122:Protein Subunits; D011947:Receptors, Antigen, B-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D014443:Tyrosine; D010047:Ovalbumin