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

1999 ◽  
Vol 190 (6) ◽  
pp. 757-764 ◽  
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.

scholarly journals T cell receptor-major histocompatibility complex class II interaction is required for the T cell response to bacterial superantigens.

1994 ◽  
Vol 180 (5) ◽  
pp. 1921-1929 ◽  
Author(s):  
N Labrecque ◽  
J Thibodeau ◽  
W Mourad ◽  
R P Sékaly
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Receptor ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Class Ii ◽  
Beta Chain ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

Bacterial and retroviral superantigens (SAGs) stimulate a high proportion of T cells expressing specific variable regions of the T cell receptor (TCR) beta chain. Although most alleles and isotypes bind SAGs, polymorphisms of major histocompatibility complex (MHC) class II molecules affect their presentation to T cells. This observation has raised the possibility that a TCR-MHC class II interaction can occur during this recognition process. To address the importance of such interactions during SAG presentation, we have used a panel of murine T cell hybridomas that respond to the bacterial SAG Staphylococcal enterotoxin B (SEB) and to the retroviral SAG Mtv-7 when presented by antigen-presenting cells (APCs) expressing HLA-DR1. Amino acid substitutions of the putative TCR contact residues 59, 64, 66, 77, and 81 on the DR1 beta chain showed that these amino acids are critical for recognition of the SAG SEB by T cells. TCR-MHC class II interactions are thus required for T cell recognition of SAG. Moreover, Mtv-7 SAG recognition by the same T cell hybridomas was not affected by these mutations, suggesting that the topology of the TCR-MHC class II-SAG trimolecular complex could be different from one TCR to another and from one SAG to another.

scholarly journals Antagonist Peptide Selects Thymocytes Expressing a Class II Major Histocompatibility Complex–restricted T Cell Receptor into the CD8 Lineage

1998 ◽  
Vol 188 (6) ◽  
pp. 1083-1089 ◽  
Author(s):  
Ariane Volkmann ◽  
Thomas Barthlott ◽  
Siegfried Weiss ◽  
Ronald Frank ◽  
Brigitta Stockinger
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Cell Differentiation ◽  
T Cell ◽  
T Cell Receptor ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Class Ii ◽  
T Cell Differentiation ◽  
Histocompatibility Complex

CD4/CD8 lineage decision is an important event during T cell maturation in the thymus. CD8 T cell differentiation usually requires corecognition of major histocompatibility complex (MHC) class I by the T cell receptor (TCR) and CD8, whereas CD4 T cells differentiate as a consequence of MHC class II recognition by the TCR and CD4. The involvement of specific peptides in the selection of T cells expressing a particular TCR could be demonstrated so far for the CD8 lineage only. We used mice transgenic for an MHC class II-restricted TCR to investigate the role of antagonistic peptides in CD4 T cell differentiation. Interestingly, antagonists blocked the development of CD4+ cells that normally differentiate in thymus organ culture from those mice, and they induced the generation of CD8+ cells in thymus organ culture from mice impaired in CD4+ cell development (invariant chain–deficient mice). These results are in line with recent observations that antagonistic signals direct differentiation into the CD8 lineage, regardless of MHC specificity.

scholarly journals Structure of a Complex of the Human α/β T Cell Receptor (TCR) HA1.7, Influenza Hemagglutinin Peptide, and Major Histocompatibility Complex Class II Molecule, HLA-DR4 (DRA*0101 and DRB1*0401)

2002 ◽  
Vol 195 (5) ◽  
pp. 571-581 ◽  
Author(s):  
Jens Hennecke ◽  
Don C. Wiley
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Receptor ◽  
Mhc Class Ii ◽  
Peptide Binding ◽  
Cell Receptor ◽  
Class Ii ◽  
Histocompatibility Complex ◽  
Peptide Binding Groove ◽  
Binding Groove

The α/β T cell receptor (TCR) HA1.7 specific for the hemagglutinin (HA) antigen peptide from influenza A virus is HLA-DR1 restricted but cross-reactive for the HA peptide presented by the allo-major histocompatibility complex (MHC) class II molecule HLA-DR4. We report here the structure of the HA1.7/DR4/HA complex, determined by X-ray crystallography at a resolution of 2.4 Å. The overall structure of this complex is very similar to the previously reported structure of the HA1.7/DR1/HA complex. Amino acid sequence differences between DR1 and DR4, which are located deep in the peptide binding groove and out of reach for direct contact by the TCR, are able to indirectly influence the antigenicity of the pMHC surface by changing the conformation of HA peptide residues at position P5 and P6. Although TCR HA1.7 is cross-reactive for HA presented by DR1 and DR4 and tolerates these conformational differences, other HA-specific TCRs are sensitive to these changes. We also find a dependence of the width of the MHC class II peptide-binding groove on the sequence of the bound peptide by comparing the HA1.7/DR4/HA complex with the structure of DR4 presenting a collagen peptide. This structural study of TCR cross-reactivity emphasizes how MHC sequence differences can affect TCR binding indirectly by moving peptide atoms.

scholarly journals Class I Major Histocompatibility Complex Anchor Substitutions Alter the Conformation of T Cell Receptor Contacts

2001 ◽  
Vol 276 (24) ◽  
pp. 21443-21449 ◽  
Author(s):  
Ashwani K. Sharma ◽  
Jennifer J. Kuhns ◽  
Shuqin Yan ◽  
Randall H. Friedline ◽  
Brian Long ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

scholarly journals An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans.

1994 ◽  
Vol 180 (3) ◽  
pp. 1097-1106 ◽  
Author(s):  
O Lantz ◽  
A Bendelac
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Mhc Class I ◽  
T Cell Receptor ◽  
Cell Subset ◽  
Cell Receptor ◽  
Class I ◽  
T Cell Subset ◽  
Alpha Chain ◽  
Histocompatibility Complex

The mouse thymus contains a mature T cell subset that is distinguishable from the mainstream thymocytes by several characteristics. It is restricted in its usage of T cell receptor (TCR) V beta genes to V beta 8, V beta 7, and V beta 2. Its surface phenotype is that of activated/memory cells. It carries the natural killer NK1.1 surface marker. Furthermore, though it consists entirely of CD4+ and CD4-8- cells, its selection in the thymus depends solely upon major histocompatibility complex (MHC) class I expression by cells of hematopoietic origin. Forced persistence of CD8, in fact, imparts negative selection. Here, we have studied the TCR repertoire of this subset and found that, whereas the beta chain V-D-J junctions are quite variable, a single invariant alpha chain V alpha 14-J281 is used by a majority of the TCRs. This surprisingly restricted usage of the V alpha 14-J281 alpha chain is dependent on MHC class I expression, but independent of the MHC haplotype. In humans, a similar unusual population including CD4-8- cells can also be found that uses a strikingly homologous, invariant alpha chain V alpha 24-JQ. Thus, this unique V alpha-J alpha combination has been conserved in both species, conferring specificity to some shared nonpolymorphic MHC class I/peptide self-ligand(s). This implies that the T cell subset that it defines has a specialized and important role, perhaps related to its unique ability to secrete a large set of lymphokines including interleukin 4, upon primary stimulation in vitro and in vivo.

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