TY - JOUR
T1 - Differential activation of T cells by antibody-modulated processing of the flanking sequences of class II-restricted peptides
AU - Fournier, Philippe
AU - Ammerlaan, Wim
AU - Ziegler, Diana
AU - Giminez, Cyrille
AU - Rabourdin-Combe, Chantal
AU - Fleckenstein, Burkhard T.
AU - Wiesmüller, Karl Heinz
AU - Jung, Günther
AU - Schneider, François
AU - Muller, Claude P.
N1 - Funding Information:
We thank Dr Berbers (RIVM, Bilthoven) for his support during the development of the mAb. Parts of this work were done by D. Z. and P. F in partial fulfilment of their MD and PhD theses The financial support of the Centre de Recherche Public-Sante, Luxembourg (CRP91/01 and CRP91/06) and the EC-Biotechnology project PL920131 is gratefully acknowledged.
PY - 1996
Y1 - 1996
N2 - Despite poor presentation of measles virus (MV) nucleoprotein (NP) by MHC class II of infected cells, NP-specific antibodies are one of the hallmarks of the early immune response against this virus. To study the influence of antibodies on processing and presentation of NP to three different T cell hybridomas, mAb recognizing distinctive linear NP epitopes were developed. Two T cell hybridomas TNP408B and TNP408 reacted with the same core epitope of NP (amino acids 383-391), but differed in their sensitivity to the flanking sequences of peptides containing this epitope. TNP408B reacted with minimal concentrations of NP when this was complexed with mAb BNP146. NP alone or saturating concentrations of other mAb did not activate this T cell. Both T cells, TNP408 and TNP408B, were similar in their sensitivity to NP in the presence of saturating concentrations of BNP146 or of appropriate peptide (NP379). TNP408 did not differ from another T cell hybridoma (TNP79) in its sensitivity to different mAb, suggesting a specificity-dependent and a specificity-independent effect of mAb. Antibody-mediated activation was attributed to FcR-mediated uptake independent of the fine specificity of the mAb. In the case of TNP408B, this effect was further enhanced by a specific effect of BNP146. While all NP-specific mAb were sufficient to enhance presentation to TNP408 and TNP79 of their respective peptides derived from processed NP, BNP146 was necessary to generate the peptides with the proper flanking sequences required by TNP408B. Since the binding site of BNP146 coincides with the T cell epitope of TNP408B (and TNP408) it is suggested that binding of this mAb modulates processing of the flanking sequences of the peptides corresponding to this epitope. This study shows that antibodies can influence the T cell response to an antigenic protein quantitatively and qualitatively by taking advantage of the sensitivity of T cells to flanking sequences of class II-restricted peptides.
AB - Despite poor presentation of measles virus (MV) nucleoprotein (NP) by MHC class II of infected cells, NP-specific antibodies are one of the hallmarks of the early immune response against this virus. To study the influence of antibodies on processing and presentation of NP to three different T cell hybridomas, mAb recognizing distinctive linear NP epitopes were developed. Two T cell hybridomas TNP408B and TNP408 reacted with the same core epitope of NP (amino acids 383-391), but differed in their sensitivity to the flanking sequences of peptides containing this epitope. TNP408B reacted with minimal concentrations of NP when this was complexed with mAb BNP146. NP alone or saturating concentrations of other mAb did not activate this T cell. Both T cells, TNP408 and TNP408B, were similar in their sensitivity to NP in the presence of saturating concentrations of BNP146 or of appropriate peptide (NP379). TNP408 did not differ from another T cell hybridoma (TNP79) in its sensitivity to different mAb, suggesting a specificity-dependent and a specificity-independent effect of mAb. Antibody-mediated activation was attributed to FcR-mediated uptake independent of the fine specificity of the mAb. In the case of TNP408B, this effect was further enhanced by a specific effect of BNP146. While all NP-specific mAb were sufficient to enhance presentation to TNP408 and TNP79 of their respective peptides derived from processed NP, BNP146 was necessary to generate the peptides with the proper flanking sequences required by TNP408B. Since the binding site of BNP146 coincides with the T cell epitope of TNP408B (and TNP408) it is suggested that binding of this mAb modulates processing of the flanking sequences of the peptides corresponding to this epitope. This study shows that antibodies can influence the T cell response to an antigenic protein quantitatively and qualitatively by taking advantage of the sensitivity of T cells to flanking sequences of class II-restricted peptides.
KW - Antibodies
KW - Measles virus
KW - Nucleoprotein
KW - Processing
UR - http://www.scopus.com/inward/record.url?scp=9544257291&partnerID=8YFLogxK
U2 - 10.1093/intimm/8.9.1441
DO - 10.1093/intimm/8.9.1441
M3 - Article
C2 - 8921422
AN - SCOPUS:9544257291
SN - 0953-8178
VL - 8
SP - 1441
EP - 1451
JO - International Immunology
JF - International Immunology
IS - 9
ER -