Mathematical, Computational and Experimental T Cell Immunology

Abstract Background: Minor histocompatibility antigens are antigenic peptides derived from normal cellular molecules which are presented in the context of major histocompatibility antigens (MHC class I and MHC class II). After an allogeneic hematopoietic stem cell transplantation (aHSCT) recipient-derived mHags can be recognized by T-cells of the transplanted immune system an mediate both a graft-versus-host disease and graft-versus- leukemia reaction. All mHags known to date have been identified by allo-reactive T-cells. Due to complex logistics needed for the establishment of such T-cell clones only a few mHags have been molecularly defined to date. Since patients with GvH develop antibodies against mHags and the presence of mHag antibodies has been shown to correlate with GvH and maintenance of remission [Miklos et al. (2005) Blood 105:2973-9] we set out to identify new mHags using SEREX the serological identification of antigens using recombinant expression cloning [Sahin et al. (1995) PNAS 92:11810-3]. Methods: Fibroblasts obtained by skin biopsies from patients with chronic GvH were propagated in vivo and used as a source to establish a cDNA library. cDNA was expressed by lambda phage in E.coli and expressed clones were screened for reactivity with antibodies in the serum of patients with chronic GvH. Positive clones were monoclonized and sequenced. The sequences were compared with known sequences using BLAST data bank. Reactive sera were compared with patient’s pre transplant serum and the serum from the donor to exclude pre-existing antibodies against (auto-)antigens expressed by the fibroblasts. Only neo-antigens recognized by the transplanted immune system were analyzed further. Results: cDNA libraries obtained from 7 patients with chronic GvH after HLA-identical stem cell transplantation were screened with the sera of these 7 patients by SEREX. Antibodies from one patient with chronic GvH were absent in the donor and the patients pre-transplant serum, reacted with c1ORF107. This constellation proves that the c1ORF107 antibodies in the patient’s serum developed after transplant and recognized c1ORF as a neo-antigen. The immunogenic c1ORF107 of the patient differed at previously described polymorphic position 275 (rs585627) with G in the recipient leading to glutamate and C in the donor leading to glutamine. The definition of the c1ORF107 epitopes eliciting a T-cell response by “reverse T-cell immunology” is currently underway. Conclusion: This study proves the principle that the analysis of the humoral immune response in patients with chronic GvH by SEREX allows for the definition of new mHags. SEREX in combination and followed by reverse T-cell immunology is a straight-forward approach which will expand considerably the number of molecularly defined mHags causing GvH in patients after allogeneic stem cell transplantation. Supported by Jose Carreras Foundation Germany

Download Full-text

A dilute bootstrap percolation: Lattice model for unresponsiveness in T-cell immunology

Journal of Statistical Physics ◽

10.1007/bf01052812 ◽

1993 ◽

Vol 73 (5-6) ◽

pp. 843-851 ◽

Cited By ~ 2

Author(s):

Marcelle Kaufman ◽

Dietrich Stauffer

Keyword(s):

T Cell ◽

Lattice Model ◽

Bootstrap Percolation ◽

T Cell Immunology

Download Full-text

T-cell immunology of the lung: maintaining the balance between host defence and immune pathology

Immunology ◽

10.1111/imm.13029 ◽

2018 ◽

Vol 156 (1) ◽

pp. 1-2

Author(s):

Daniel M. Altmann

Keyword(s):

T Cell ◽

Host Defence ◽

Immune Pathology ◽

T Cell Immunology

Download Full-text

TCRdb: a comprehensive database for T-cell receptor sequences with powerful search function

Nucleic Acids Research ◽

10.1093/nar/gkaa796 ◽

2020 ◽

Vol 49 (D1) ◽

pp. D468-D474 ◽

Cited By ~ 1

Author(s):

Si-Yi Chen ◽

Tao Yue ◽

Qian Lei ◽

An-Yuan Guo

Keyword(s):

T Cell ◽

T Cell Receptor ◽

Length Distribution ◽

Cell Types ◽

Cell Receptor ◽

Search Function ◽

Tcr Repertoire ◽

Tcr Diversity ◽

Clinical Conditions ◽

T Cell Immunology

Abstract T cells and the T-cell receptor (TCR) repertoire play pivotal roles in immune response and immunotherapy. TCR sequencing (TCR-Seq) technology has enabled accurate profiling TCR repertoire and currently a large number of TCR-Seq data are available in public. Based on the urgent need to effectively re-use these data, we developed TCRdb, a comprehensive human TCR sequences database, by a uniform pipeline to characterize TCR sequences on TCR-Seq data. TCRdb contains more than 277 million highly reliable TCR sequences from over 8265 TCR-Seq samples across hundreds of tissues/clinical conditions/cell types. The unique features of TCRdb include: (i) comprehensive and reliable sequences for TCR repertoire in different samples generated by a strict and uniform pipeline of TCRdb; (ii) powerful search function, allowing users to identify their interested TCR sequences in different conditions; (iii) categorized sample metadata, enabling comparison of TCRs in different sample types; (iv) interactive data visualization charts, describing the TCR repertoire in TCR diversity, length distribution and V-J gene utilization. The TCRdb database is freely available at http://bioinfo.life.hust.edu.cn/TCRdb/ and will be a useful resource in the research and application community of T cell immunology.

Download Full-text