Immunodominance

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Immunodominance ( English immunodominance ) refers to the phenomenon that in the course of an adaptive immune response , some parts of a pathogen trigger a stronger immune reaction than others. Therefore, after a vaccination or a survived infection , an immune reaction is only detectable for some epitopes that are typical for pathogens .

principle

Immune dominance can occur in epitopes recognized by B cells and T cells . It is used to concentrate an immune response to a few epitopes of a pathogen. The epitopes are determined by epitope mapping . The dominance of a presented epitope depends, among other things, on the affinity of the bond between epitope and MHC, the affinity of the bond between epitope and T-cell receptor or B-cell receptor and on the previous proteolysis of the antigens into the individual epitopes. The better the epitope fits the respective MHC and the more MHC-bound epitopes are presented on a cell, the stronger the subsequent immune reaction. The previous immune reactions have an influence on the immunodominant epitopes, described as antigenic sin .

Humoral immunodominance

Epitopes for the humoral immune response are presented by MHC II on professional antigen-presenting cells and bound by CD4- positive T helper cells , whereupon the formation of antibodies is increased. Antigens circulating in the blood and in the lymph can also be bound directly by antibodies or by the B-cell receptor , which also increases antibody production in B-cells. MHCII-presented epitopes are extracellular origin, while the antigens are of an antigen presenting cell by endocytosis added and endosomal and lysosomal proteases such as furin and cathepsins broken down into short peptides, some of which can bind to MHC II and then to the cell surface for presentation exozytiert be . The affinity of the binding of the epitope to the MHCII depends on the respective MHCII subtype, while the part of the antibody that binds to the epitope ( paratope ) is variable.

Cellular immunodominance

Epitopes for the cellular immune response are presented by MHC I on antigen-presenting cells and bound by CD8- positive cytotoxic T cells , whereupon the presenting cell is lysed . MHCI-presented epitopes mainly originate from inside the cell. Among other things, they are broken down by the proteasome , introduced into the endoplasmic reticulum via the antigen peptide transporter , bind to MHCI and are secreted on the cell surface . Humans each have an individual set of the different MHC variants (HLA) and all variants have different binding preferences for epitopes. As a result, an epitope can induce a strong immune response in some people with a correspondingly well-binding HLA molecule, but not in other people without well-binding HLA. Type B HLA molecules tend to present a wider range of different peptides than HLA-A molecules. The paratope of the T cell receptor is variable. The avidity of the variable part of the T cell receptor for its epitope determines the amount of cytotoxic T cells formed in succession. However, too high an avidity for an epitope can lead to apoptosis in the cytotoxic T cell .

Individual evidence

  1. ↑ a b A. Akram, RD Inman: Immunodominance: a pivotal principle in host response to viral infections. In: Clinical immunology (Orlando, Fla.). Volume 143, number 2, May 2012, pp. 99-115, doi : 10.1016 / j.clim.2012.01.015 , PMID 22391152 .
  2. ↑ C. Perrault: Experimental and Applied Immunotherapy. Humana, 2011. ISBN 978-1-60761-980-2 . Pp. 195-206.
  3. ↑ A. Kim, S. Sadegh-Nasseri: Determinants of immunodominance for CD4 T cells. In: Current opinion in immunology. Volume 34, June 2015, pp. 9–15, doi : 10.1016 / j.coi.2014.12.005 , PMID 25576665 , PMC 4444386 (free full text).
  4. ^ W. Kastenmuller, G. Gasteiger, JH Gronau, R. Baier, R. Ljapoci, DH Busch, I. Drexler: Cross-competition of CD8 + T cells shapes the immunodominance hierarchy during boost vaccination. In: The Journal of experimental medicine. Volume 204, number 9, September 2007, pp. 2187-2198, doi : 10.1084 / jem.20070489 , PMID 17709425 , PMC 2118691 (free full text).
  5. ↑ J. Dinter, E. Duong, NY Lai, MJ Berberich, G. Kourjian, E. Bracho-Sanchez, D. Chu, H. Su, SC Zhang, S. Le Gall: Variable processing and cross-presentation of HIV by dendritic cells and macrophages shapes CTL immunodominance and immune escape. In: PLoS pathogens. Volume 11, number 3, March 2015, p. E1004725, doi : 10.1371 / journal.ppat.1004725 , PMID 25781895 , PMC 4364612 (free full text).
  6. ↑ S. Duan, VA Meliopoulos, JL McClaren, XZ Guo, CJ Sanders, HS Smallwood, RJ Webby, SL Schultz-Cherry, PC Doherty, PG Thomas: Diverse heterologous primary infections radically alter immunodominance hierarchies and clinical outcomes following H7N9 influenza challenge in mice. In: PLoS pathogens. Volume 11, number 2, February 2015, p. E1004642, doi : 10.1371 / journal.ppat.1004642 , PMID 25668410 , PMC 4335497 (free full text).
  7. ↑ CJ Kim, DR Parkinson, F. Marincola: Immunodominance across HLA polymorphism: implications for cancer immunotherapy. In: Journal of immunotherapy (Hagerstown, Md.: 1997). Volume 21, Number 1, January 1998, pp. 1-16, PMID 9456431 .
  8. ^ IM Schellens, I. Hoof, HD Meiring, SN Spijkers, MC Poelen, JA van Gaans-van den Brink, K. van der Poel, AI Costa, CA van Els, D. van Baarle, C. Kesmir: Comprehensive Analysis of the Naturally Processed Peptide Repertoire: Differences between HLA-A and B in the Immunopeptidome. In: PloS one. Volume 10, number 9, 2015, p. E0136417, doi : 10.1371 / journal.pone.0136417 , PMID 26375851 , PMC 4574158 (free full text).
  9. ↑ T. Cukalac, J. Chadderton, W. Zeng, JG Cullen, WT Kan, PC Doherty, DC Jackson, SJ Turner, NL La Gruta: The influenza virus-specific CTL immunodominance hierarchy in mice is determined by the relative frequency of high -avidity T cells. In: Journal of Immunology (Baltimore, Md.: 1950). Volume 192, Number 9, May 2014, pp. 4061-4068, doi : 10.4049 / jimmunol.1301403 , PMID 24696232 .
  10. ↑ S. Dalla Santa, A. Merlo, S. Bobisse, E. Ronconi, D. Boldrin, G. Milan, V. Barbieri, O. Marin, A. Facchinetti, G. Biasi, R. Dolcetti, P. Zanovello, A. Rosato: Functional avidity-driven activation-induced cell death shapes CTL immunodominance. In: Journal of Immunology (Baltimore, Md.: 1950). Volume 193, Number 9, November 2014, pp. 4704-4711, doi : 10.4049 / jimmunol.1303203 , PMID 25246498 .