Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Inferring the “Primordial Immune Complex”: Origins of MHC Class I and Antigen Receptors Revealed by Comparative Genomics

Yuko Ohta, Masanori Kasahara, Timothy D. O’Connor and Martin F. Flajnik
J Immunol September 6, 2019, ji1900597; DOI: https://doi.org/10.4049/jimmunol.1900597
Yuko Ohta
*Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masanori Kasahara
†Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timothy D. O’Connor
‡Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201;
§Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201;
¶Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, 21201; and
‖Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Timothy D. O’Connor
Martin F. Flajnik
*Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF
Loading

Key Points

  • Emergence of class I/II and Ag receptor genes is proposed via comparative genomics.

  • Nonrearranging Ag receptor–like genes were identified in MHC paralogous regions.

  • Ancient translocation of an MHC genomic region including CD1 genes was discovered and named “MHCtrans.”

Abstract

Comparative analyses suggest that the MHC was derived from a prevertebrate “primordial immune complex” (PIC). PIC duplicated twice in the well-studied two rounds of genome-wide duplications (2R) early in vertebrate evolution, generating four MHC paralogous regions (predominantly on human chromosomes [chr] 1, 6, 9, 19). Examining chiefly the amphibian Xenopus laevis, but also other vertebrates, we identified their MHC paralogues and mapped MHC class I, AgR, and “framework” genes. Most class I genes mapped to MHC paralogues, but a cluster of Xenopus MHC class Ib genes (xnc), which previously was mapped outside of the MHC paralogues, was surrounded by genes syntenic to mammalian CD1 genes, a region previously proposed as an MHC paralogue on human chr 1. Thus, this gene block is instead the result of a translocation that we call the translocated part of the MHC paralogous region (MHCtrans). Analyses of Xenopus class I genes, as well as MHCtrans, suggest that class I arose at 1R on the chr 6/19 ancestor. Of great interest are nonrearranging AgR-like genes mapping to three MHC paralogues; thus, PIC clearly contained several AgR precursor loci, predating MHC class I/II. However, all rearranging AgR genes were found on paralogues derived from the chr 19 precursor, suggesting that invasion of a variable (V) exon by the RAG transposon occurred after 2R. We propose models for the evolutionary history of MHC/TCR/Ig and speculate on the dichotomy between the jawless (lamprey and hagfish) and jawed vertebrate adaptive immune systems, as we found genes related to variable lymphocyte receptors also map to MHC paralogues.

Footnotes

  • This project was supported by National Institutes of Health Grants AI140326-26 and AI02877 to Y.O. and M.F.F.

  • The online version of this article contains supplemental material.

  • Received May 23, 2019.
  • Accepted August 2, 2019.
  • Copyright © 2019 by The American Association of Immunologists, Inc.
PreviousNext
Back to top

In this issue

The Journal of Immunology: 206 (3)
The Journal of Immunology
Vol. 206, Issue 3
1 Feb 2021
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Inferring the “Primordial Immune Complex”: Origins of MHC Class I and Antigen Receptors Revealed by Comparative Genomics
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Inferring the “Primordial Immune Complex”: Origins of MHC Class I and Antigen Receptors Revealed by Comparative Genomics
Yuko Ohta, Masanori Kasahara, Timothy D. O’Connor, Martin F. Flajnik
The Journal of Immunology September 6, 2019, ji1900597; DOI: 10.4049/jimmunol.1900597

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Inferring the “Primordial Immune Complex”: Origins of MHC Class I and Antigen Receptors Revealed by Comparative Genomics
Yuko Ohta, Masanori Kasahara, Timothy D. O’Connor, Martin F. Flajnik
The Journal of Immunology September 6, 2019, ji1900597; DOI: 10.4049/jimmunol.1900597
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
  • Figures & Data
  • Info & Metrics
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting
  • Functional Interactions of Common Allotypes of Rhesus Macaque FcγR2A and FcγR3A with Human and Macaque IgG Subclasses
  • Revisiting the Pig IGHC Gene Locus in Different Breeds Uncovers Nine Distinct IGHG Genes
Show more IMMUNOGENETICS

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • Public Access
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2021 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606