The mechanism underlying T cell help for induction of an antigen-specific in vivo humoral immune response to intact Streptococcus pneumoniae is dependent on the type of antigen.
Little is known concerning the role of T cells in regulating an anti-polysaccharide Ig response to an intact pathogen. We previously reported that the in vivo Ig responses to Streptococcus pneumoniae (strain R36A), specific for pneumococcal surface protein A (PspA) and for the phosphorylcholine (PC) determinant of C-polysaccharide, were both dependent on TCR-alphabeta(+) T cells and B7-dependent costimulation, although only PspA-specific memory was generated. In this report, we show that the T cell help underlying these two Ag-specific Ig responses is distinct. Using H-Y-specific T cell transgenic mice made "nonleaky" by crossing with mice genetically deficient for TCR-alpha, we demonstrate that the T cell help for the anti-PC, in contrast to the anti-PspA, response is TCR-nonspecific and occurs normally in the absence of germinal center formation, although it is still dependent on B7-dependent costimulation. Consistent with these data, we demonstrate, using cathepsin S(-/-) mice, that although the anti-PC response is largely dependent on CD4(+) T cells, there is a reduced (or lack of) dependence, relative to the anti-PspA response, on the generation of new peptide-MHC class II complexes. In this regard, the T cell help for an optimal anti-PC response is delivered more rapidly than that required for an optimal anti-PspA response. Collectively, these data demonstrate a novel accelerated TCR-nonspecific B7-dependent form of T cell help for augmenting a polysaccharide-specific Ig response to an intact bacterium without the generation of memory.
Wu
Zheng-Qi
ZQ
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Shen
Yi
Y
Khan
Abdul Q
AQ
Chu
Ching-Liang
CL
Riese
Richard
R
Chapman
Harold A
HA
Kanagawa
Osami
O
Snapper
Clifford M
CM
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000502:physiology; D001426:Bacterial Proteins / Q000276:immunology*; D002403:Cathepsins / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D010767:Phosphorylcholine / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D000907:Antibodies, Bacterial; D018122:B7-1 Antigen; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D011948:Receptors, Antigen, T-Cell; C051592:pneumococcal surface protein A; D010767:Phosphorylcholine; D002403:Cathepsins; C028217:cathepsin S