Importantly, the proteomic identification within the outer membrane immunogen and the bioinformatic prediction of surface localization was confirmed for a subset of these proteins by surface-specific crosslinking. The isolated cross-linked surface protein complex induced protection equal to that of the native outer membrane immunogen. The first is that AM779 is immunologically subdominant in vaccinates immunized with either the outer membrane immunogen or the cross-linked surface complex. The importance of sub-dominant epitopes in immune protection has been clearly established for several viral pathogens,. The second hypothesis is that immunization with recombinant AM779 will result in significantly greater enhancement of specific B and T cell responses to AM779 as compared to those induced by the more complex immunogens. If accepted, this would indicate that it is the membrane context of minor proteins such as AM779 that results in their sub-dominance rather than an intrinsic lack of epitopes. The third is that AM779 will generate recall responses upon A. marginale challenge. This would support that despite lower abundance in the outer membrane, there is sufficient antigen in the native context to stimulate the anamnestic response—a requirement for sub-dominant antigens to function in vaccines. Fourth, we tested whether immune responses to AM779, induced either by immunization with AM779 alone or by immunization with outer membranes or surface complexes, correlated with protection against challenge. Herein we present the results of testing these four hypotheses and discuss the significance of the results in vaccine development for A. marginale and related pathogens. The third stated hypothesis, that AM779 responses are recalled upon presentation of native antigen during actual infection, was also accepted. The second hypothesis, that immunization with recombinant AM779 generates significantly higher responses than when in the membrane context, was accepted for the T cell responses but not for the IgG2 antibody responses. The significantly greater T cell responses when animals were immunized individually with AM779 as compared to animals immunized with the outer membranes were observed independent of the MHC class II haplotypes of vaccinates. This is consistent with the presence of multiple immunogenic epitopes in AM779 that can be presented via the diverse MHC class II molecules represented within the immunized population. These results suggest that for AM779 relative abundance in the immunogen may be deterministic for T cell responses rather than intrinsic epitope structure being responsible for sub-dominance relative to major components such as Msp2 and Msp3. The anamnestic response upon challenge with A. marginale indicates that while of low abundance in the bacterial outer membrane, there is sufficient antigen to stimulate memory B lymphocytes, cells which due to high affinity SJN 2511 immunoglobulin receptors induced by prior immunization have a much lower antigen requirement for reactivation. Interestingly, the AM779 specific recall response was detected earlier in the AM779 vaccinates than in the outer membrane vaccinates, suggesting that there may have been differences in the vaccine induced priming between the two groups. This is consistent with the more uniform AM779 specific T cell response in the AM779 vaccinates which may provide more robust help upon re-exposure to the antigen.