scholarly journals Mating preferences can drive expansion or contraction of major histocompatibility complex gene family

2020 ◽  
Vol 287 (1921) ◽  
pp. 20192706
Author(s):  
Piotr Bentkowski ◽  
Jacek Radwan
Keyword(s):  
Major Histocompatibility Complex ◽  
Gene Family ◽  
Random Mating ◽  
Major Histocompatibility Complex Gene ◽  
Major Histocompatibility ◽  
Mating Preferences ◽  
Histocompatibility Complex ◽  
Mhc Diversity ◽  
Mechanistic Basis

Major histocompatibility complex (MHC)-based mating rules can evolve as a way to avoid inbreeding or to increase offspring immune competence. While the role of mating preference in shaping the MHC diversity in vertebrates has been acknowledged, its impact on individual MHC diversity has not been considered. Here, we use computer simulations to investigate how simple mating rules favouring MHC-dissimilar partners affect the evolution of the number of MHC variants in individual genomes, accompanying selection for resistance to parasites. We showed that the effect of such preferences could sometimes be dramatic. If preferences are aimed at avoiding identical alleles, the equilibrium number of MHC alleles is much smaller than under random mating. However, if the mating rule minimizes the ratio of shared to different alleles in partners, MHC number is higher than under random mating. Additionally, our simulations revealed that a negative correlation between the numbers of MHC variants in mated individuals can arise from simple rules of MHC-disassortative mating. Our results reveal unexpected potential of MHC-based mating preferences to drive MHC gene family expansions or contractions and highlight the need to study the mechanistic basis of such preferences, which is currently poorly understood.

scholarly journals Low major histocompatibility complex diversity in the Tasmanian devil predates European settlement and may explain susceptibility to disease epidemics

2013 ◽  
Vol 9 (1) ◽  
pp. 20120900 ◽  
Author(s):  
Katrina Morris ◽  
Jeremy J. Austin ◽  
Katherine Belov
Keyword(s):  
Major Histocompatibility Complex ◽  
Tasmanian Devil ◽  
Major Histocompatibility ◽  
European Settlement ◽  
Low Genetic Diversity ◽  
Histocompatibility Complex ◽  
Devil Facial Tumour Disease ◽  
History Of ◽  
Mhc Diversity ◽  
Disease Epidemics

The Tasmanian devil ( Sarcophilus harrisii ) is at risk of extinction owing to the emergence of a contagious cancer known as devil facial tumour disease (DFTD). The emergence and spread of DFTD has been linked to low genetic diversity in the major histocompatibility complex (MHC). We examined MHC diversity in historical and ancient devils to determine whether loss of diversity is recent or predates European settlement in Australia. Our results reveal no additional diversity in historical Tasmanian samples. Mainland devils had common modern variants plus six new variants that are highly similar to existing alleles. We conclude that low MHC diversity has been a feature of devil populations since at least the Mid-Holocene and could explain their tumultuous history of population crashes.

scholarly journals The major histocompatibility complex-restricted antigen receptor on T cells. II. Role of the L3T4 product.

1983 ◽  
Vol 158 (4) ◽  
pp. 1077-1091 ◽  
Author(s):  
P Marrack ◽  
R Endres ◽  
R Shimonkevitz ◽  
A Zlotnik ◽  
D Dialynas ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Cell Receptor ◽  
Surface Expression ◽  
High Avidity ◽  
Low Doses ◽  
Major Histocompatibility ◽  
Histocompatibility Complex

We have examined the role of the murine homologue of Leu-3 T4, L3T4, in recognition of antigen in association with products of the major histocompatibility complex (Ag/MHC) by murine T cell hybridomas. A series of ovalbumin (OVA)/I-Ad-specific T cell hybridomas were ranked in their sensitivity to Ag/I by measuring their ability to respond to low doses of OVA, or their sensitivity to inhibition by anti-I-Ad antibodies. T cell hybridomas with low apparent avidity for OVA/I-Ad, i.e. that did not respond well to low concentrations of OVA and were easily inhibited by anti-I-Ad, were also easily inhibited by anti-L3T4 antibodies. The reverse was true for T cell hybridomas with apparent high avidity for Ag/MHC. We found that the presence of low doses of anti-L3T4 antibodies caused T cell hybridomas to respond less well to low doses of Ag, and to be more easily inhibited by anti-I-Ad antibodies. These results suggested that the role of the L3T4 molecule is to increase the overall avidity of the reaction between T cells and Ag-presenting cells. In support of this idea was the discovery of several L3T4- subclones of one of our L3T4+ T cell hybridomas, D0.11.10. The L3T4- subclones had the same amount of receptor for OVA/I-Ad as their L3T4+ parent, as detected by an anti-receptor monoclonal antibody. The L3T4- subclones, however, responded less well to low doses of OVA, and were more easily inhibited by anti-I-Ad antibodies than their L3T4/ parent. These results showed that the L3T4 molecule was not required for surface expression of, or functional activity of, the T cell receptor for Ag/MHC. The L3T4 molecule did, however, increase the sensitivity with which the T cell reacted with Ag/MHC on Ag-presenting cells.

scholarly journals The Role of Peptides in T Cell Alloreactivity Is Determined by Self–Major Histocompatibility Complex Molecules

2000 ◽  
Vol 191 (5) ◽  
pp. 805-812 ◽  
Author(s):  
Reinhard Obst ◽  
Nikolai Netuschil ◽  
Karsten Klopfer ◽  
Stefan Stevanović ◽  
Hans-Georg Rammensee
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Target Cells ◽  
Major Histocompatibility ◽  
Complex Molecules ◽  
Mhc Molecules ◽  
Histocompatibility Complex ◽  
Alloreactive T Cells

By analyzing T cell responses against foreign major histocompatibility complex (MHC) molecules loaded with peptide libraries and defined self- and viral peptides, we demonstrate a profound influence of self-MHC molecules on the repertoire of alloreactive T cells: the closer the foreign MHC molecule is related to the T cell's MHC, the higher is the proportion of peptide-specific, alloreactive (“allorestricted”) T cells versus T cells recognizing the foreign MHC molecule without regard to the peptide in the groove. Thus, the peptide repertoire of alloreactive T cells must be influenced by self-MHC molecules during positive or negative thymic selection or peripheral survival, much like the repertoire of the self-restricted T cells. In consequence, allorestricted, peptide-specific T cells (that are of interest for clinical applications) are easier to obtain if T cells and target cells express related MHC molecules.

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