Inclusion group systems and cis-trans effects in responses controlled by the two complementing Ir-GLphi genes

Area of Science:

• Immunogenetics
• Molecular immunology
• Polymer science

Background:

• Immune responses to synthetic polypeptides are genetically controlled.
• H-linked immune response (Ir) genes play a crucial role in regulating T-cell mediated immunity.
• Understanding the genetic basis of immune responses to defined antigens is key to immunomodulation.

Purpose of the Study:

• To investigate the genetic control of immune responses to three random linear terpolymers of L-amino acids.
• To determine the H-2 gene distribution patterns associated with immune responses to these terpolymers.
• To explore the role of cis and trans configurations of immune response genes.

Main Methods:

• Synthesis and characterization of three random linear terpolymers: poly-(glu57, lys38, tyr5), poly-(glu51, lys34, tyr15,), and poly-(glu53, lys36, phe11).
• Immunization of different mouse strains (H-2 congenic) with the terpolymers.
• Analysis of antibody production and T-cell proliferation as measures of immune response.
• Genetic mapping of immune response loci.

Main Results:

• Each terpolymer elicited immune responses controlled by two dominant H-linked Ir genes.
• Distinct H-2 gene distributions were observed for the immune responses to the three terpolymers.
• These H-2 patterns were found to be part of a single inclusion group system.
• Alpha- and beta-genes controlling the response were dominant, with optimal interaction in the cis configuration.

Conclusions:

• The immune response to these terpolymers is governed by a pair of dominant H-linked Ir genes.
• A single inclusion group system explains the H-2 distributions observed.
• The cis configuration of alpha- and beta-genes significantly enhances immune gene interactions, highlighting the importance of the cis-trans effect in immune regulation.