Restricted and conserved T-cell repertoires involved in allorecognition of class II major histocompatibility complex.

ABSTRACTKnowledge of naturally processedBordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presentedB. pertussisCD4+T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4+T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the naturalB. pertussisepitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition ofB. pertussis. A more complete understanding of hallmarks inB. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies.

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Class II major histocompatibility complex-restricted T cell function in CD4-deficient mice

European Journal of Immunology ◽

10.1002/eji.1830240942 ◽

1994 ◽

Vol 24 (9) ◽

pp. 2213-2218 ◽

Cited By ~ 69

Author(s):

Amin Rahemtulla ◽

Thomas M. Kündig ◽

Arumugabadiv Narendran ◽

Martin F. Bachmann ◽

Michael Julius ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

Cell Function ◽

Class Ii ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

T Cell Function ◽

Deficient Mice

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Specificity of T cell clones for antigen and autologous major histocompatibility complex products determines specificity for foreign major histocompatibility complex products.

Journal of Experimental Medicine ◽

10.1084/jem.158.2.428 ◽

1983 ◽

Vol 158 (2) ◽

pp. 428-437 ◽

Cited By ~ 40

Author(s):

S R Abromson-Leeman ◽

H Cantor

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

Molecular Mimicry ◽

Class Ii ◽

Major Histocompatibility ◽

T Cell Clones ◽

Complex Products ◽

Mhc Molecules ◽

Histocompatibility Complex ◽

Cell Clones

We have analyzed a panel of T cell clones that corecognize defined epitopes of the insulin molecule in association with Ia for their patterns of recognition of alloantigens. A striking correlation is observed between recognition of the I-Ab gene product and cow insulin alpha loop and recognition of I-Eu of the PL/J haplotype. These results are consistent with the notion that reactions to foreign major histocompatibility complex (MHC) products reflect molecular mimicry by foreign class II antigens of 'physiologic' complexes formed by autologous class II MHC molecules and antigen.

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Greatly reduced lymphoproliferation in lpr mice lacking major histocompatibility complex class I.

Journal of Experimental Medicine ◽

10.1084/jem.181.2.641 ◽

1995 ◽

Vol 181 (2) ◽

pp. 641-648 ◽

Cited By ~ 58

Author(s):

M A Maldonado ◽

R A Eisenberg ◽

E Roper ◽

P L Cohen ◽

B L Kotzin

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

Class Ii ◽

T Cell Subsets ◽

Cell Surface Receptor ◽

Class I ◽

Major Histocompatibility ◽

Gamma Delta ◽

Histocompatibility Complex

Mice homozygous for the lpr gene have a defect in fas (CD95), a cell surface receptor that belongs to the tumor necrosis factor receptor family and that mediates apoptosis. This genetic abnormality results in lymphoproliferation characterized by the accumulation of CD4-CD8- (double negative [DN]) T cells, autoantibody production, and background strain-dependent, end-organ disease. Our previous results suggested that major histocompatibility complex (MHC) class I may be involved in the development of DN cells. To test this hypothesis, we derived C57BL/6-lpr/lpr (B6/lpr) mice that were deficient for the beta 2-microglobulin gene (beta 2m lpr) and had no detectable class I expression. At 6 mo of age, compared with B6/lpr littermates with normal class I genes, these mice showed greatly reduced lymphadenopathy, mostly due to a dramatic decrease in the number of DN cells. Significant changes in the percentage of other T cell subsets were noted, but only gamma/delta+ T cells showed a marked increase in both percentage and absolute numbers. Analysis of T cell receptor V beta expression of the remaining DN T cells in beta 2m -lpr mice showed a shift to a CD4-like repertoire from a CD8-like repertoire in control B6/lpr mice, indicating that a small MHC class II selected DN population was unmasked in lpr mice lacking class I. We also found that the production of immunoglobulin G (IgG) autoantibodies (antichromatin and anti-single stranded DNA), total IgG and IgG2a, but not total IgM or IgM rheumatoid factor, was significantly reduced in the beta 2m -lpr mice. This work suggests that >90% of DN T cells in lpr mice are derived from the CD8 lineage and are selected on class I. However, a T cell subset selected on class II and T cells expressing gamma/delta are also affected by the lpr defect and become minor components of the aberrant DN population.

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Immunogenicity and tolerogenicity of self-major histocompatibility complex peptides.

Journal of Experimental Medicine ◽

10.1084/jem.172.5.1341 ◽

1990 ◽

Vol 172 (5) ◽

pp. 1341-1346 ◽

Cited By ~ 62

Author(s):

G Benichou ◽

P A Takizawa ◽

P T Ho ◽

C C Killion ◽

C A Olson ◽

...

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

Class Ii ◽

Class I ◽

Major Histocompatibility ◽

Autoreactive T Cells ◽

Mhc Molecules ◽

Histocompatibility Complex ◽

Self Tolerance

Mechanisms involved in self-antigen processing and presentation are crucial in understanding the induction of self-tolerance in the thymus. We examined the immunogenicity of determinants from major histocompatibility complex (MHC) molecules that are expressed in the thymus and have tested peptides derived from the polymorphic regions of class I and class II molecules. We found that two peptides corresponding to NH2 termini of the class II alpha and beta chains (Ak alpha 1-18 and Ak beta 1-16) could bind to self-Ak molecules with high affinity and, surprisingly, were immunogenic in that they could elicit strong proliferative T cell responses in B10.A mice (Ak, Ek). Neonatal injection of peptide Ak beta 1-16 resulted in complete unresponsiveness to this peptide at 8 wk of age showing that these T cells were susceptible to tolerance induction. We have also tested certain class I MHC peptides and showed that some can interact efficiently with class II MHC peptides to induce an autoreactive T cell proliferative response. Among these class I peptides is one (Dd 61-85) that has the capacity to bind to self-Ia without being immunogenic, and therefore represents an MHC determinant that had induced thymic self-tolerance. We conclude that some self-MHC molecules can be processed into peptides that can be presented in the context of intact class II molecules at the surface of antigen-presenting cells. Autoreactive T cells recognizing optimally processed self-peptide/MHC complexes are eliminated during development, whereas other potentially autoreactive T cells escape clonal inactivation or deletion. Incomplete tolerance to self-antigens enriches the T cell repertoire despite the fact that such T cells may eventually become involved in autoimmune disease.

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