scholarly journals The Genomic Organisation of the TRA/TRD Locus Validates the Peculiar Characteristics of Dromedary δ-Chain Expression

2021 ◽  
Author(s):  
Serafina Massari ◽  
Giovanna Linguiti ◽  
Francesco Giannico ◽  
Pietro D'Addabbo ◽  
Salvatrice Maria Ciccarese ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Receptors ◽  
Somatic Hypermutation ◽  
Genomic Structure ◽  
Mammalian Species ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
Germline Genes ◽  
Genomic Organisation

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) ac-count for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage from the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR alpha (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

scholarly journals The Genomic Organisation of the TRA/TRD Locus Validates the Peculiar Characteristics of Dromedary δ-Chain Expression

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 544
Author(s):  
Serafina Massari ◽  
Giovanna Linguiti ◽  
Francesco Giannico ◽  
Pietro D’Addabbo ◽  
Salvatrice Ciccarese ◽  
...  
Keyword(s):  
T Cells ◽  
Somatic Hypermutation ◽  
Genomic Structure ◽  
Mammalian Species ◽  
Γδ T Cells ◽  
Antigen Binding Site ◽  
Germline Genes ◽  
Δ Chain ◽  
Genomic Organisation

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) account for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage of the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR α (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site.

scholarly journals The mycoplasma surface proteins MIB and MIP promote the dissociation of the antibody-antigen interaction

2021 ◽  
Vol 7 (10) ◽  
pp. eabf2403
Author(s):  
Pierre Nottelet ◽  
Laure Bataille ◽  
Geraldine Gourgues ◽  
Robin Anger ◽  
Carole Lartigue ◽  
...  
Keyword(s):  
Surface Proteins ◽  
Mycoplasma Species ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
Fab Fragment ◽  
Cryo Electron Microscopy ◽  
Antigen Complex ◽  
Antigen Interaction ◽  
Immunoglobulin Binding

Mycoplasma immunoglobulin binding (MIB) and mycoplasma immunoglobulin protease (MIP) are surface proteins found in the majority of mycoplasma species, acting sequentially to capture antibodies and cleave off their VH domains. Cryo–electron microscopy structures show how MIB and MIP bind to a Fab fragment in a “hug of death” mechanism. As a result, the orientation of the VL and VH domains is twisted out of alignment, disrupting the antigen binding site. We also show that MIB-MIP has the ability to promote the dissociation of the antibody-antigen complex. This system is functional in cells and protects mycoplasmas from antibody-mediated agglutination. These results highlight the key role of the MIB-MIP system in immunity evasion by mycoplasmas through an unprecedented mechanism, and open exciting perspectives to use these proteins as potential tools in the antibody field.

Role of the mobility of antigen binding site in high affinity antibody elucidated by surface plasmon resonance

2016 ◽  
Vol 161 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Natsuki Fukuda ◽  
Yoshiaki Suwa ◽  
Makiyo Uchida ◽  
Yoshihiro Kobashigawa ◽  
Hideshi Yokoyama ◽  
...  
Keyword(s):  
Surface Plasmon Resonance ◽  
Binding Site ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
High Affinity

scholarly journals Inhibition of T-antigen-binding cells by idiotypic antisera.

1977 ◽  
Vol 146 (3) ◽  
pp. 766-778 ◽  
Author(s):  
C A Prange ◽  
J Fiedler ◽  
D E Nitecki ◽  
C J Bellone
Keyword(s):  
T Cells ◽  
Lymph Node ◽  
Guinea Pig ◽  
T Cell Receptors ◽  
Binding Assay ◽  
T Antigen ◽  
Antigen Binding ◽  
Variable Regions ◽  
Heterologous System ◽  
Lymph Node Cells

Shared idiotypy between B- and T-cell receptors specific for the antigen L-tyrosine-p-azophenyltrimethylammonium [tyr(TMA)] was studied in an antigen-binding assay using idiotypic antisera. These idiotypic reagents were prepared by inoculation of rabbits with purified anti-tyr(TMA) antibody raised in strain 13 guinea pigs. The antisera blocked 78-83% of the antigen-binding T cells (T-ABC) and 50-55% of the antigen-binding B cells (B-ABC) from tyr(TMA)-immune strain 13 and outbred lymph node cells (LNC). An excess of normal guinea pig Ig in the ABC assay did not affect the ability of the idiotypic antisera to block T- and B-ABC. Nylon wool-passed tyr(TMA)-immune LNC were trypsin treated resulting in a 75% loss of T-ABC. The trypsin-treated population was then cultured for 16 h which resulted in a return of T-ABC to 92% of pretrypsin values. 77% of these regenerated T-ABC could be blocked with idiotypic antisera. Specificity of the idiotypic antisera was tested in L-tyrosine-p-azobenzenearsonate-immune guinea pig LNC. Neither T- nor B-ABC were blocked in this heterologous system. Further blocking experiments were performed to characterize the nature of the T-ABC receptor. A variety of anti-Ig reagents, some of which block B-ABC, do not inhibit T-ABC suggesting that variable regions on T cells are not linked to Ig Constant regions.

Sequence-Based Evidence for Antigen Selection in Mantle Cell Lymphoma: Remarkable Immunoglobulin Gene Repertoire Biases, Stereotyped Antigen-Binding Sites and Recurrent Hypermutations in Certain Subsets.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1933-1933 ◽  
Author(s):  
Anastasia Hadzidimitriou ◽  
Andreas Agathagelidis ◽  
Fiona Murray ◽  
Marie-Helene Delfau-Larue ◽  
Nikos Darzentas ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Somatic Hypermutation ◽  
Antigen Binding ◽  
Gene Repertoire ◽  
Immunoglobulin Gene ◽  
Antigen Binding Site ◽  
Ighv Gene ◽  
Mantle Cell

Abstract Abstract 1933 Poster Board I-956 According to the 2008 WHO Classification, mantle cell lymphoma (MCL) most likely derives from neoplastic transformation of a peripheral B cell of the inner mantle zone, mostly of naïve pre-germinal center type. Analysis of the immunoglobulin (IG) repertoire in MCL has revealed a bias in IG heavy variable (IGHV) gene usage and a predominance of unmutated rearrangements, with a variable minor proportion of cases carrying mutated IGHV genes (according to the 98% identity cutoff). However, limited knowledge exists regarding antigen-binding site sequence restrictions or specific somatic hypermutation (SHM) patterns in MCL. We examined the productive IGHV-D-J rearrangements of 651 MCL cases (including 398 cases from the European MCL Network), the largest series to date. We confirm and significantly extend previous observations that the IGHV gene repertoire is remarkably biased, with only three genes accounting for 40.3% of cases (IGHV3-21, 16.7%; IGHV4-34, 15.3%; IGHV1-8: 8.3%). Using bioinformatics approaches previously applied to CLL, biased associations of certain IGHV, IGHD and IGHJ genes with restricted (stereotyped) heavy complementarity-determining regions (HCDR3s) were identified in 68/651 cases (10.4%). Overall, 24 subsets of cases with stereotyped HCDR3s were recognized. Eight of 24 subsets included 3-7 cases each (“confirmed”), while the remaining 16 subsets included two cases each and were considered “provisional”. Stereotyped HCDR3s were found predominantly amongst rearrangements utilizing the IGHV3-21 and IGHV4-34 genes and the IGHJ6 gene. Notably, the MCL HCDR3 stereotypes identified here were distinct from those previously reported in CLL. Based on SHM analysis, the sequences were divided into three groups: (i) truly unmutated (100% germline identity, GI): 189/651 sequences (29.2%); (ii) minimally/borderline mutated (98-99.9% GI): 306/651 sequences (47%); and (iii) mutated (<98% GI): 155/651 sequences (23.8%), of which 93 had a GI<97%. In keeping with previous reports, the IGHV gene repertoire of the three identity groups differed considerably. For instance, the IGHV3-21 gene was used by 7% of rearrangements with <98% identity vs. 22.8% of rearrangements with 100% identity. In contrast, the IGHV3-23 gene was over-represented among mutated rearrangements (26.4%). Shared (“stereotyped”) amino acid (AA) changes across the entire IGHV gene sequence were identified for certain groups of sequences, especially those utilizing the IGHV1-8, IGHV3-21 and IGHV3-23 genes. A comparison to published series from other entities, in particular CLL, revealed that several stereotyped mutations identified in MCL were “disease-biased”. Importantly, stereotyped AA changes were also observed in the borderline or minimally mutated groups, indicating that even a low level of mutations may be functionally relevant. In conclusion, MCL is characterized by a highly distinctive IG gene repertoire with restricted HCDR3s and very precisely targeted and, probably, functionally driven SHM, strongly implying a role for antigen-driven selection of the clonogenic progenitors. Based on the evidence presented here, an antigen-driven origin of MCL could be envisaged, at least for subsets of cases. Disclosures: No relevant conflicts of interest to declare.

The structure of the antigen-binding site of immunoglobulins and T-cell receptors

1995 ◽  
Vol 146 (4-5) ◽  
pp. 277-290 ◽  
Author(s):  
G.A. Bentley ◽  
G. Boulot ◽  
R.A. Mariuzza
Keyword(s):  
T Cell ◽  
Binding Site ◽  
T Cell Receptors ◽  
Antigen Binding ◽  
Antigen Binding Site ◽  
Cell Receptors

scholarly journals TCR-dependent differentiation of thymic Foxp3+ cells is limited to small clonal sizes

2009 ◽  
Vol 206 (10) ◽  
pp. 2121-2130 ◽  
Author(s):  
Monica W.L. Leung ◽  
Shiqian Shen ◽  
Juan J. Lafaille
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Foxp3 Expression ◽  
Bone Marrow Chimera ◽  
High Affinity ◽  
Intrathymic Injection ◽  
Deficient Mice ◽  
Selection Of

Numerous studies have highlighted the importance of high-affinity interactions between T cell receptors (TCRs) and their ligands in the selection of Foxp3+ regulatory T cells (T reg cells). To determine the role of the TCR in directing T cells into the Foxp3+ lineage, we generated transgenic (Tg) mice expressing TCRs from Foxp3+ cells. Initial analyses of the TCR Tg mice crossed with RAG-deficient mice showed that the percentage of Foxp3+ cells was very low. However, intrathymic injection and bone marrow chimera experiments showed a saturable increase of the Foxp3+ population when T reg TCR Tg cells were present in low numbers. Furthermore, when analyzing whole thymi of T reg TCR Tg RAG-deficient mice, we found significantly more Foxp3+ cells than in conventional T cell TCR Tg mice. Our results indicate that although the TCR has an instructive role in determining Foxp3 expression, selection of Foxp3+ individual clones in the thymus is limited by a very small niche.

The role of chromatin organizer Satb1 in shaping TCR repertoire in adult thymus

Genome ◽  
2021 ◽  
Author(s):  
Delong Feng ◽  
Zhaoqiang Li ◽  
Litao Qin ◽  
Bingtao Hao
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Essential Role ◽  
T Cell Development ◽  
Cdr3 Length ◽  
Tcr Repertoire ◽  
The Universe ◽  
Adult Thymus

T cells recognize the universe of foreign antigens with a diverse repertoire of T cell receptors generated by V (D)J recombination. Special AT-rich binding protein 1 (Satb1) is a chromatin organizer that plays an essential role in T cell development. The previous study showed that Satb1 regulates the re-induction of recombinase Rag1 and Rag2 in CD4+CD8+ thymocytes, affecting the secondary rearrangement of the Tcra gene. Here, we detected the repertoires of four TCR genes, Tcrd, Tcrg, Tcrb, and Tcra in the adult thymus, and explored the role of the Satb1 in shaping the TCR repertoires. We observed a strong bias in the V and J gene usages of the Tcrd and Tcrg repertoires in WT and Satb1-deleted thymocytes. Satb1 deletion had few effects on the V(D)J rearrangement and repertoire of the Tcrg, Tcrd, and Tcrb genes. The Tcra repertoire was severely impaired in Satb1-deleted thymocytes, while the primary rearrangement was relatively normal. We also found the CDR3 length of TCRα chain was significantly longer in Satb1-deleted thymocytes, which can be explained by the strong bias of the proximal Jα usage. Our results showed that Satb1 plays an essential role in shaping TCR repertoires in αβ T cells.

scholarly journals Three-dimensional localization of T-cell receptors in relation to microvilli using a combination of superresolution microscopies

2016 ◽  
Vol 113 (40) ◽  
pp. E5916-E5924 ◽  
Author(s):  
Yunmin Jung ◽  
Inbal Riven ◽  
Sara W. Feigelson ◽  
Elena Kartvelishvily ◽  
Kazuo Tohya ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Receptors ◽  
Three Dimensional ◽  
Spatial Relation ◽  
Protein Distribution ◽  
Cell Receptors ◽  
Human T Cells ◽  
Antigen Presenting

Leukocyte microvilli are flexible projections enriched with adhesion molecules. The role of these cellular projections in the ability of T cells to probe antigen-presenting cells has been elusive. In this study, we probe the spatial relation of microvilli and T-cell receptors (TCRs), the major molecules responsible for antigen recognition on the T-cell membrane. To this end, an effective and robust methodology for mapping membrane protein distribution in relation to the 3D surface structure of cells is introduced, based on two complementary superresolution microscopies. Strikingly, TCRs are found to be highly localized on microvilli, in both peripheral blood human T cells and differentiated effector T cells, and are barely found on the cell body. This is a decisive demonstration that different types of T cells universally localize their TCRs to microvilli, immediately pointing to these surface projections as effective sensors for antigenic moieties. This finding also suggests how previously reported membrane clusters might form, with microvilli serving as anchors for specific T-cell surface molecules.

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