A role for major histocompatibility complex (MHC) class II molecules in MHC class I presentation and CD8 T cell priming

This study brings new information on major histocompatibility complex (MHC) class III sub-region genes in Old World camels and integrates current knowledge of the MHC region into a comprehensive overview for Old World camels. Out of the MHC class III genes characterized, TNFA and the LY6 gene family showed high levels of conservation, characteristic for MHC class III loci in general. For comparison, an MHC class II gene TAP1, not coding for antigen presenting molecules but functionally related to MHC antigen presenting functions was studied. TAP1 had many SNPs, even higher than the MHC class I and II genes encoding antigen presenting molecules. Based on this knowledge and using new camel genomic resources, we constructed an improved genomic map of the entire MHC region of Old World camels. The MHC class III sub-region shows a standard organization similar to that of pig or cattle. The overall genomic structure of the camel MHC is more similar to pig MHC than to cattle MHC. This conclusion is supported by differences in the organization of the MHC class II sub-region, absence of functional DY genes, different organization of MIC genes in the MHC class I sub-region, and generally closer evolutionary relationships of camel and porcine MHC gene sequences analyzed so far.

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Major histocompatibility complex (MHC) fragment numbers alone – in Atlantic cod and in general - do not represent functional variability

F1000Research ◽

10.12688/f1000research.15386.1 ◽

2018 ◽

Vol 7 ◽

pp. 963 ◽

Cited By ~ 2

Author(s):

Johannes M. Dijkstra ◽

Unni Grimholt

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

Mhc Class Ii ◽

Fish Species ◽

Teleost Fish ◽

Class Ii ◽

Class I ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Speciation Rates

This correspondence concerns a publication by Malmstrøm et al. in Nature Genetics in October 2016. Malmstrøm et al. made an important contribution to fish phylogeny research by using low-coverage genome sequencing for comparison of 66 teleost (modern bony) fish species, with 64 of those 66 belonging to the species-rich clade Neoteleostei, and with 27 of those 64 belonging to the order Gadiformes. For these 66 species, Malmstrøm et al. estimated numbers of genes belonging to the major histocompatibility complex (MHC) class I lineages U and Z and concluded that in teleost fish these combined numbers are positively associated with, and a driving factor of, the rates of establishment of new fish species (speciation rates). They also claimed that functional genes for the MHC class II system molecules MHC IIA, MHC IIB, CD4 and CD74 were lost in early Gadiformes. Our main criticisms are (1) that the authors did not provide sufficient evidence for presence or absence of intact functional MHC class I or MHC class II system genes, (2) that they did not discuss that an MHC subpopulation gene number alone is a very incomplete measure of MHC variance, and (3) that the MHC system is more likely to reduce speciation rates than to enhance them. We conclude that their new model of MHC class I evolution, reflected in their title “Evolution of the immune system influences speciation rates in teleost fish”, is unsubstantiated. In addition, we explain that their “pinpointing” of the functional loss of the MHC class II system and all the important MHC class II system genes to the onset of Gadiformes is preliminary, because they did not sufficiently investigate the species at the clade border.

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Myofiber Expression of Class I Major Histocompatibility Complex Accompanied by CD8+ T-cell-associated Myofiber Injury in a Case of Canine Polymyositis

Veterinary Pathology ◽

10.1354/vp.39-4-512 ◽

2002 ◽

Vol 39 (4) ◽

pp. 512-515 ◽

Cited By ~ 9

Author(s):

T. Morita ◽

A. Shimada ◽

S. Yashiro ◽

T. Takeuchi ◽

Y. Hikasa ◽

...

Keyword(s):

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

Mhc Class I ◽

Plasma Cells ◽

Early Stage ◽

Cd8 T Cell ◽

Class I ◽

Major Histocompatibility ◽

Histocompatibility Complex

A 7-year-old female Labrador Retriever dog showed extreme muscular weakness, muscle wasting, dysbasia, and mild dysphagia. An elevated value of creatine kinase (335 IU/liter) in the serum was detected. Electromyographic findings included increased insertional activity, fibrillation potentials, and bizarre high-frequency repetitive potentials. Histopathologic examination of skeletal muscles revealed myofiber necrosis and phagocytosis, regeneration of myofibers, and perivascular, perimysial, and endomysial infiltrations of lymphocytes, macrophages and plasma cells. Immunohistochemical evaluation demonstrated that infiltrative cells in the early stage of myositis were CD8+ T-cells and that an increased expression of major histocompatibility complex (MHC) class I was apparent on the surface of nonnecrotic muscle fibers. In contrast, many CD3+ cells (T cells) and HLA-DR-positive macrophages and B lymphocytes were found in the severely affected areas. These results suggest that both expression of MHC class I and CD8+ T-cell infiltration may play an important role in initiation of myositis. These histopathologic findings resemble those reported in naturally occurring polymyositis in humans.

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Major histocompatibility complex independent clonal T cell anergy by direct interaction of Staphylococcus aureus enterotoxin B with the T cell antigen receptor.

Journal of Experimental Medicine ◽

10.1084/jem.175.6.1493 ◽

1992 ◽

Vol 175 (6) ◽

pp. 1493-1499 ◽

Cited By ~ 92

Author(s):

C R Hewitt ◽

J R Lamb ◽

J Hayball ◽

M Hill ◽

M J Owen ◽

...

Keyword(s):

Staphylococcus Aureus ◽

T Cells ◽

Major Histocompatibility Complex ◽

T Cell ◽

Mhc Class Ii ◽

Direct Interaction ◽

Class Ii ◽

Cell Antigen ◽

Histocompatibility Complex ◽

Mhc Class Ii Molecules

The Staphylococcal enterotoxin superantigens stimulate vigorous responses in T cells bearing certain T cell antigen receptor (TCR) V beta regions. In addition to activation, these superantigens also impart negative signals to T cells resulting in a profound state of unresponsiveness or anergy. The Staphylococcus aureus enterotoxins (SE) B and C2 bind to a closely related site on major histocompatibility complex (MHC) human leukocyte antigen (HLA)-DR1 molecules. Only SEB, however, interacts with the TCR V beta 3 region of HA1.7, a human HLA-DR1 restricted T cell clone specific for influenza haemagglutinin. In competition experiments, we demonstrated that the induction of anergy in HA1.7 by SEB is unaffected by the presence of SEC2. These results suggest that SEB-induced anergy is MHC independent and involves a direct interaction between the TCR and SEB. To resolve definitively whether SEB binds directly to T cells in the absence of MHC class II molecules, the cDNAs encoding the HA1.7 TCR were transfected into an MHC class II-negative human T cell line. The addition of SEB to these transfectants resulted in the downregulation of cell surface TCR expression, an increase in the concentration of intracellular calcium ions, the production of lymphokines, and reduced responsiveness to a subsequent challenge with SEB. We conclude that SEB interacts directly with the TCR in the absence of cointeraction with MHC class II molecules, and that this interaction may induce anergy in HA1.7.

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Major histocompatibility complex class II-restricted presentation of an internally synthesized antigen displays cell-type variability and segregates from the exogenous class II and endogenous class I presentation pathways.

Journal of Experimental Medicine ◽

10.1084/jem.178.1.73 ◽

1993 ◽

Vol 178 (1) ◽

pp. 73-85 ◽

Cited By ~ 44

Author(s):

G E Loss ◽

C G Elias ◽

P E Fields ◽

R K Ribaudo ◽

M McKisic ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class Ii ◽

Transmembrane Protein ◽

Class Ii ◽

Class I ◽

Major Histocompatibility ◽

Membrane Expression ◽

Histocompatibility Complex ◽

Presentation Pathway ◽

Mhc Class Ii Molecules

Although reported examples of endogenous antigen (Ag) presentation by major histocompatibility complex (MHC) class II molecules have increased, the mechanisms governing this process remain poorly defined. In this communication, we describe an experimental system designed to examine the mechanisms governing class II presentation of internal Ag. Our target peptide is processed from a transmembrane protein constitutively expressed by a variety of nucleated cells (MHC class I, H-2Ld), is naturally displayed by MHC class II molecules in vivo, and is recognized by a class II-restricted, CD4+ T cell hybridoma. Our results indicate that presentation of the Ld target Ag is independent of its plasma membrane expression, may not involve endosomal proteolysis, and thus may be distinct from the classically defined class II presentation pathway. In addition, the observations that Ld presentation does not require a functional TAP-1 complex, is not blocked by invariant chain, and cannot utilize cytoplasmic forms of H-2Ld, suggest that a classical class I pathway is not involved in this presentation event. Finally, our data suggest that different cofactors participate in MHC class II presentation of exogenous and endogenous Ag, and that disparate Ag presenting cells, such as B, T, and pancreatic islet cells, may differentially express these two class II pathways of Ag presentation.

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The Final Maturation of at Least Some Single-Positive Cd4hiThymocytes Does Not Require T Cell Receptor–Major Histocompatibility Complex Contact

Journal of Experimental Medicine ◽

10.1084/jem.190.6.757 ◽

1999 ◽

Vol 190 (6) ◽

pp. 757-764 ◽

Cited By ~ 9

Author(s):

Ruben Dyall ◽

Janko Nikolić-Z̆ugić

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

T Cell Receptor ◽

Mhc Class Ii ◽

Cell Receptor ◽

Class Ii ◽

Class I ◽

Histocompatibility Complex ◽

Final Maturation ◽

Single Positive

The majority (∼70%) of postselection CD4+ single-positive (SP) thymocytes are CD8loCD4hi. These cells express very low levels of CD8, undetectable by flow cytofluorimetric (FCM) analysis, but sufficiently high to allow purification by panning. Unlike the fully mature CD8−CD4hi thymocytes, which account for the remaining ∼30% of the SP CD4+ thymocytes, CD8loCD4hi cells are functionally immature and short-lived unless they receive an unidentified maturation signal from the thymus. In this study, we tested the hypothesis that this signal is provided by a T cell receptor (TCR)–major histocompatibility complex (MHC) class II interaction. Using intrathymic transfer, we show that the immature CD8loCD4hi cells could complete their intrathymic maturation and populate the peripheral lymphoid organs in the absence of MHC class II (and class I) molecules. Furthermore, in mice devoid of class II (and class I) molecules, the progeny of CD8loCD4hi cells was long-lived and functionally reactive to allogeneic class II molecules, although their numbers in the spleen and the mesenteric lymph node were ∼40–50% lower than those in class II+ mice 5 mo after transfer. Control experiments demonstrated that the surviving cells did not originate from the contaminating mature thymocytes. These results demonstrate that the final maturation, proliferation, and peripheral survival (up to 5 mo) of at least some postselection CD4+ SP cells do not require the TCR–MHC class II interaction. They also indicate that the TCR–MHC class II interaction(s) required for the intrathymic development of long-lived CD4+ SP cells occurs before the CD4hi SP stage of development.

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CD8+ T cell response to Mls-1a determinants involves major histocompatibility complex class II molecules.

Journal of Experimental Medicine ◽

10.1084/jem.173.3.779 ◽

1991 ◽

Vol 173 (3) ◽

pp. 779-782 ◽

Cited By ~ 14

Author(s):

Y Chvatchko ◽

H R MacDonald

Keyword(s):

Major Histocompatibility Complex ◽

T Cell ◽

Mhc Class Ii ◽

T Cell Responses ◽

Cd8 T Cell ◽

Class Ii ◽

T Cell Response ◽

Major Histocompatibility ◽

Cell Responses ◽

Histocompatibility Complex

Recent studies indicate that both CD4+ and CD8+ T lymphocytes proliferate in vitro in response to Mls-1a-encoded determinants. Using both immunogenetic and antibody blocking approaches we show here that Mls-1a responses of both subsets require expression of major histocompatibility complex (MHC) class II molecules (I-A and/or I-E) by the stimulator cells. Furthermore, CD8+ T cell responses to Mls-1a/class II MHC do not require (and are in fact inhibited by) the presence of functional CD8 molecules. Taken together, our data underscore the dramatic differences between CD8+ T cell responses to conventional peptide antigens as opposed to "superantigens" such as Mls-1a.

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