Mycobacterium tuberculosis in the adjuvant modulates the balance of Th immune response to self-antigen of the CNS without influencing a "core" repertoire of specific T cells.
In the present study, we use modified CDR3 beta-chain spectratyping (immunoscope) to dissect the effect of Mycobacterium tuberculosis (MT)-derived proteins on individual PLP139-151-specific cells in the SJL mouse strain. In this model, the immunoscope technique allows the characterization of a public TCR that involves rearrangement of Vbeta10 and Jbeta1.1 and a semi-private TCR characterized by rearrangement of Vbeta4 and Jbeta1.6. Both rearrangements are specific for PLP139-151 and sequences of the CDR3 region of the two beta-chains show a conserved motif for the public rearrangement and related but more variable sequences for the semi-private rearrangement. MT-derived proteins promote increase of IFN-gamma-secreting cells. However, we observe that the presence and amount of MT used during immunization have no effect on the frequency of usage, polarization and in vivo expansion of cells carrying the studied rearrangements. Rather, the strong Th1-promoting effect of adjuvant is possibly due to recruitment toward Th1 of a wider spectrum of TCR repertoires. Therefore, instead of having a comprehensive effect on the entire repertoire, MT modulates the immune response by affecting a subset of antigen-specific T cells whose polarization can be adapted to the environment. This step establishes the final balance between Th1 and Th2 and may be essential for the enhancement or protection of disease.
Nicolò
Chiara
C
Institute of General Pathology, Catholic University, Rome, Italy.
Di Sante
Gabriele
G
Orsini
Massimiliano
M
Rolla
Simona
S
Columba-Cabezas
Sandra
S
Romano Spica
Vincenzo
V
Ricciardi
Gualtiero
G
Chan
Bosco Man Chu
BM
Ria
Francesco
F
D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D001324:Autoantigens; D001426:Bacterial Proteins; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151); D007371:Interferon-gamma