scholarly journals Functional diversification gave rise to allelic specialization in a rice NLR immune receptor pair

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Juan Carlos De la Concepcion ◽  
Javier Vega Benjumea ◽  
Aleksandra Bialas ◽  
Ryohei Terauchi ◽  
Sophien Kamoun ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plant Immunity ◽  
Single Amino Acid ◽  
Hybrid Necrosis ◽  
Amino Acid Polymorphism ◽  
Plant Populations ◽  
Hypersensitive Cell Death ◽  
Pathogen Invasion ◽  
Immune Receptors ◽  
Single Amino Acid Polymorphism

Cooperation between receptors from the NLR superfamily is important for intracellular activation of immune responses. NLRs can function in pairs that, upon pathogen recognition, trigger hypersensitive cell death and stop pathogen invasion. Natural selection drives specialization of host immune receptors towards an optimal response, whilst keeping a tight regulation of immunity in the absence of pathogens. However, the molecular basis of co-adaptation and specialization between paired NLRs remains largely unknown. Here, we describe functional specialization in alleles of the rice NLR pair Pik that confers resistance to strains of the blast fungus Magnaporthe oryzae harbouring AVR-Pik effectors. We revealed that matching pairs of allelic Pik NLRs mount effective immune responses whereas mismatched pairs lead to autoimmune phenotypes, a hallmark of hybrid necrosis in both natural and domesticated plant populations. We further showed that allelic specialization is largely underpinned by a single amino acid polymorphism that determines preferential association between matching pairs of Pik NLRs. These results provide a framework for how functionally linked immune receptors undergo co-adaptation to provide an effective and regulated immune response against pathogens. Understanding the molecular constraints that shape paired NLR evolution has implications beyond plant immunity given that hybrid necrosis can drive reproductive isolation.

scholarly journals Functional diversification gave rise to allelic specialization in a rice NLR immune receptor pair

2021 ◽  
Author(s):  
Juan Carlos De la Concepcion ◽  
Javier Vega Benjumea ◽  
Aleksandra Bialas ◽  
Ryohei Terauchi ◽  
Sophien Kamoun ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plant Immunity ◽  
Single Amino Acid ◽  
Hybrid Necrosis ◽  
Amino Acid Polymorphism ◽  
Plant Populations ◽  
Hypersensitive Cell Death ◽  
Pathogen Invasion ◽  
Immune Receptors ◽  
Single Amino Acid Polymorphism

Cooperation between receptors from the NLR superfamily is important for intracellular activation of immune responses. NLRs can function in pairs that, upon pathogen recognition, trigger hypersensitive cell death and stop pathogen invasion. Natural selection drives specialization of host immune receptors towards an optimal response, whilst keeping a tight regulation of immunity in the absence of pathogens. However, the molecular basis of co-adaptation and specialization between paired NLRs remains largely unknown. Here, we describe functional specialization in alleles of the rice NLR pair Pik that confers resistance to strains of the blast fungus Magnaporthe oryzae harbouring AVR-Pik effectors. We revealed that matching pairs of allelic Pik NLRs mount effective immune responses whereas mismatched pairs lead to autoimmune phenotypes, a hallmark of hybrid necrosis in both natural and domesticated plant populations. We further showed that allelic specialization is largely underpinned by a single amino acid polymorphism that determines preferential association between matching pairs of Pik NLRs. These results provide a framework for how functionally linked immune receptors undergo co-adaptation to provide an effective and regulated immune response against pathogens. Understanding the molecular constraints that shape paired NLR evolution has implications beyond plant immunity given that hybrid necrosis can drive reproductive isolation.

scholarly journals A single amino acid polymorphism in the glycosyltransferase CpsK defines four Streptococcus suis serotypes

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
David Roy ◽  
Taryn B. T. Athey ◽  
Jean-Philippe Auger ◽  
Guillaume Goyette-Desjardins ◽  
Marie-Rose Van Calsteren ◽  
...  
Keyword(s):  
Amino Acid ◽  
Streptococcus Suis ◽  
Single Amino Acid ◽  
Amino Acid Polymorphism ◽  
Single Amino Acid Polymorphism

Cysteine 138 mutation in HIV-1 Nef from patients with delayed disease progression

Sexual Health ◽  
2006 ◽  
Vol 3 (4) ◽  
pp. 281 ◽  
Author(s):  
Martin Tolstrup ◽  
Alex L. Laursen ◽  
Jan Gerstoft ◽  
Finn S. Pedersen ◽  
Lars Ostergaard ◽  
...  
Keyword(s):  
Disease Progression ◽  
Immune Modulation ◽  
Treatment Strategies ◽  
Disease Status ◽  
Allelic Frequency ◽  
Single Amino Acid ◽  
Amino Acid Polymorphism ◽  
Cell Decline ◽  
Single Amino Acid Polymorphism ◽  
Hiv 1

Background: The nef gene from HIV-1 has been shown to be an important pathogenic factor when considering development of AIDS. Detection of nef variants with an effect on immune modulation is important to understand HIV-1 pathogenesis and has possible impact on treatment strategies. Methods: The nef gene of HIV-1 isolates from patients in a long-term non-progressor (LTNP) cohort and a slow-progressor (SP) cohort (n = 11) was analysed and compared with isolates from a control patient group of progressors (n = 18). Most of the patients with delayed disease progression had extensive medical records, providing an insight into the LTNP disease profile and allowing for the stratification of patients based on their CD4 cell decline. Results: In sequences from nine patients, most of the functional domains of HIV-1 Nef appeared intact, and no major deletions were observed to possibly account for an effect on the delayed disease status. However, the results demonstrate a high incidence of a single amino acid polymorphism (cysteine 138) in HIV-1 Nef. The allelic frequency of cysteine 138 between the delayed disease progression group and the progressor group was found to be statistically significant (P = 0.0139). The phylogeny of isolates was investigated and the variants harbouring the cysteine 138 mutation clustered independently. Conclusion: The present study describes a viral genetic polymorphism related to AIDS disease progression. The polymorphism (cysteine 138) has previously been reported to confer decreased viral replication (Premkumar DR, et al. AIDS Res Hum Retroviruses 1996; 12(4): 337–45). A sequence database search for comparative mutations revealed a high frequency of cysteine 138 in patients with reported SP AIDS.

scholarly journals Identification, immunomodulatory activity, and immunogenicity of the major helper T-cell epitope on the K blood group antigen

Blood ◽  
2012 ◽  
Vol 119 (23) ◽  
pp. 5563-5574 ◽  
Author(s):  
Jillian Stephen ◽  
Lindsay S. Cairns ◽  
Wendy J. Pickford ◽  
Mark A. Vickers ◽  
Stanislaw J. Urbaniak ◽  
...  
Keyword(s):  
Amino Acid ◽  
Blood Group ◽  
Mhc Class Ii ◽  
Cell Epitope ◽  
Single Amino Acid ◽  
Immunomodulatory Activity ◽  
Amino Acid Polymorphism ◽  
C Terminus ◽  
Single Amino Acid Polymorphism ◽  
Linked Suppression

Abstract The K blood group remains an important target in hemolytic disease of the newborn (HDN), with no immune prophylaxis available. The aim was to characterize the Th response to K as a key step in designing specific immunotherapy and understanding the immunogenicity of the Ag. PBMCs from K-negative women who had anti-K Abs after incompatible pregnancy, and PBMCs from unimmunized controls, were screened for proliferative responses to peptide panels spanning the K or k single amino acid polymorphism. A dominant K peptide with the polymorphism at the C terminus elicited proliferation in 90% of alloimmunized women, and it was confirmed that responding cells expressed helper CD3+CD4+ and “memory” CD45RO+ phenotypes, and were MHC class II restricted. A relatively high prevalence of background peptide responses independent of alloimmunization may contribute to K immunogenicity. First, cross-reactive environmental Ag(s) pre-prime Kell-reactive Th cells, and, second, the K substitution disrupts an N-glycosylation motif, allowing the exposed amino acid chain to stimulate a Th repertoire that is unconstrained by self-tolerance in K-negative individuals. The dominant K peptide was effective in inducing linked suppression in HLA-transgenic mice and can now be taken forward for immunotherapy to prevent HDN because of anti-K responses.

scholarly journals A Single-Amino-Acid Polymorphism in Reovirus Protein  2 Determines Repression of Interferon Signaling and Modulates Myocarditis

2011 ◽  
Vol 86 (4) ◽  
pp. 2302-2311 ◽  
Author(s):  
S. C. Irvin ◽  
J. Zurney ◽  
L. S. Ooms ◽  
J. D. Chappell ◽  
T. S. Dermody ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Interferon Signaling ◽  
Amino Acid Polymorphism ◽  
Single Amino Acid Polymorphism

scholarly journals Natural HLA Class I Polymorphism Controls the Pathway of Antigen Presentation and Susceptibility to Viral Evasion

2004 ◽  
Vol 200 (1) ◽  
pp. 13-24 ◽  
Author(s):  
Danielle Zernich ◽  
Anthony W. Purcell ◽  
Whitney A. Macdonald ◽  
Lars Kjer-Nielsen ◽  
Lauren K. Ely ◽  
...  
Keyword(s):  
Hla Class I ◽  
Class I ◽  
Single Amino Acid ◽  
Amino Acid Polymorphism ◽  
Cell Repertoire ◽  
Hla Polymorphism ◽  
Viral Interference ◽  
Presentation Pathway ◽  
Peptide Loading ◽  
Single Amino Acid Polymorphism

HLA class I polymorphism creates diversity in epitope specificity and T cell repertoire. We show that HLA polymorphism also controls the choice of Ag presentation pathway. A single amino acid polymorphism that distinguishes HLA-B*4402 (Asp116) from B*4405 (Tyr116) permits B*4405 to constitutively acquire peptides without any detectable incorporation into the transporter associated with Ag presentation (TAP)-associated peptide loading complex even under conditions of extreme peptide starvation. This mode of peptide capture is less susceptible to viral interference than the conventional loading pathway used by HLA-B*4402 that involves assembly of class I molecules within the peptide loading complex. Thus, B*4402 and B*4405 are at opposite extremes of a natural spectrum in HLA class I dependence on the PLC for Ag presentation. These findings unveil a new layer of MHC polymorphism that affects the generic pathway of Ag loading, revealing an unsuspected evolutionary trade-off in selection for optimal HLA class I loading versus effective pathogen evasion.

scholarly journals Hypomorphic Glycosyltransferase Alleles and Recoding at Contingency Loci Influence Glycan Microheterogeneity in the Protein Glycosylation System of Neisseria Species

2012 ◽  
Vol 194 (18) ◽  
pp. 5034-5043 ◽  
Author(s):  
Camilla Johannessen ◽  
Michael Koomey ◽  
Bente Børud
Keyword(s):  
Protein Glycosylation ◽  
Single Amino Acid ◽  
Bacterial Protein ◽  
Amino Acid Polymorphism ◽  
Content Type ◽  
Reading Frame ◽  
Neisseria Species ◽  
Natural Systems ◽  
Single Amino Acid Polymorphism ◽  
Contingency Loci

ABSTRACTAs more bacterial protein glycosylation systems are identified and characterized, a central question that arises is, what governs the prevalence of particular glycans associated with them? In addition, accumulating evidence shows that bacterial protein glycans can be subject to the phenomenon of microheterogeneity, in which variant glycan structures are found at specific attachment sites of a given glycoprotein. Although factors underlying microheterogeneity in reconstituted expression systems have been identified and modeled, those impacting natural systems largely remain enigmatic. On the basis of a sensitive and specific glycan serotyping system, microheterogeneity has been reported for the broad-spectrum,O-linked protein glycosylation system in species within the genusNeisseria. To elucidate the mechanisms involved, a genetic approach was used to identify a hypomorphic allele ofpglA(encoding the PglA galactosyltransferase) as a significant contributor to simultaneous expression of multiple glycoforms. Moreover, this phenotype was mapped to a single amino acid polymorphism in PglA. Further analyses revealed that manypglAphase-off variants (containing out-of-frame configurations in simple nucleotide repeats within the open reading frame) were associated with disproportionally high levels of theN,N′-diacetylbacillosamine–Gal disaccharide glycoform generated by PglA. This phenotype is emblematic of nonstandard decoding involving programmed ribosomal frameshifting and/or programmed transcriptional realignment. Together, these findings provide new information regarding the mechanisms of neisserial protein glycan microheterogeneity and the anticipatory nature of contingency loci.

scholarly journals Finding new structural and sequence attributes to predict possible disease association of single amino acid polymorphism (SAP)

2007 ◽  
Vol 23 (12) ◽  
pp. 1444-1450 ◽  
Author(s):  
Z.-Q. Ye ◽  
S.-Q. Zhao ◽  
G. Gao ◽  
X.-Q. Liu ◽  
R. E. Langlois ◽  
...  
Keyword(s):  
Amino Acid ◽  
Disease Association ◽  
Single Amino Acid ◽  
Amino Acid Polymorphism ◽  
Single Amino Acid Polymorphism
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